The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the...The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the columnar structures and fine martensite formation.This study investigated the effect of carbon nanotubes(CNTs)addition on the microstructure and mechanical properties of grade 1 CP-Ti(Gr-1)during the laser powder bed fusion(L-PBF)process.A minute amount of 0.2%mass fraction(wt%)CNTs addition resulted in a high yield strength of approximately 700 MPa and exceptional ductility of 25.7%.Therein,a portion of the CNTs dissolved in the matrix as solute atoms,contributing to solution strengthening,while others were transformed into Ti C_(x)through an in situ reaction with the Ti matrix.Furthermore,the addition of CNTs resulted in the formation of a larger fraction of equiaxed grains and increased the activity of basal and prismatic slip systems.Hence,Gr-1 with CNTs exhibited significantly increased ductility while maintaining a high strength comparable to that of Gr-1 without CNTs.The insights gained from this study provide a novel approach for designing strong and ductile Ti alloys for AM.展开更多
Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix re...Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix remodeling.Although KBD and OA share overlapping clinical and pathological features,key differences exist in their etiology and disease progression.KBD preferentially affects children aged 3-12 years,whereas OA predominantly affects older individuals between the age of 40-60 years.KBD cartilage necrosis originates in the deep layers of the epiphyseal plate and articular cartilage,progressing toward the cartilage surface.In contrast,OA cartilage destruction initiates at the articular cartilage surface and gradually progresses to expose the subchondral bone[1,2].展开更多
BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditional...BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditionally,the primary treatment has been laparoscopic appendectomy(LA).CASE SUMMARY A 63-year-old female presented with changes in bowel habits.Colonoscopy revealed an ileocecal LST.The patient underwent endoscopic submucosal dissection.Postoperative follow-up colonoscopy revealed mucosal elevation at the appendiceal orifice,with pathology confirming tubular adenoma.Abdominal computed tomography indicated a suspicious appendiceal tumor,leading to LA with partial cecectomy.The postoperative recovery was uneventful.At the 1-year follow-up,colonoscopy revealed no evidence of tumor recurrence.CONCLUSION Ileocecal LSTs with appendiceal tubular adenomas are traditionally treated with LA.endoscopic submucosal dissection can also yield favorable outcomes.展开更多
Deep learning networks are increasingly exploited in the field of neuronal soma segmentation.However,annotating dataset is also an expensive and time-consuming task.Unsupervised domain adaptation is an effective metho...Deep learning networks are increasingly exploited in the field of neuronal soma segmentation.However,annotating dataset is also an expensive and time-consuming task.Unsupervised domain adaptation is an effective method to mitigate the problem,which is able to learn an adaptive segmentation model by transferring knowledge from a rich-labeled source domain.In this paper,we propose a multi-level distribution alignment-based unsupervised domain adaptation network(MDA-Net)for segmentation of 3D neuronal soma images.Distribution alignment is performed in both feature space and output space.In the feature space,features from different scales are adaptively fused to enhance the feature extraction capability for small target somata and con-strained to be domain invariant by adversarial adaptation strategy.In the output space,local discrepancy maps that can reveal the spatial structures of somata are constructed on the predicted segmentation results.Then thedistribution alignment is performed on the local discrepancies maps across domains to obtain a superior discrepancy map in the target domain,achieving refined segmentation performance of neuronal somata.Additionally,after a period of distribution align-ment procedure,a portion of target samples with high confident pseudo-labels are selected as training data,which assist in learning a more adaptive segmentation network.We verified the superiority of the proposed algorithm by comparing several domain adaptation networks on two 3D mouse brain neuronal somata datasets and one macaque brain neuronal soma dataset.展开更多
Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits o...Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.展开更多
Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and it...Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible molecular mechanisms. Methods The expressions of Caspase 8 mRNA and protein were detected with RT-PCR and Western blot analysis. The effects of IFNγ, TRAIL, IFNγ ＋ TRAIL, IFNγ ＋ Caspase 8 inhibitor ＋ TRAIL, IFNγ ＋ cisplatin ＋ TRAIL, and IFNγ ＋ etoposide ＋ TRAIL on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. The relative Caspase 8 activity was measured with colorimetric assay. Results Caspase 8 was undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and protein was found after treatment with IFNγ. SH-SY5Y ceils themselves were not sensitive to TRAIL, but those expressing Caspase 8 after treatment with IFNγ were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8 was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y cells in IFNγ ＋ TRAIL group was significantly higher than those of control group, IFNγ group, TRAIL group, and inhibitor group （ P 〈 0. 01 ）. There was no significant difference among IFNγ ＋ TRAIL group, IFNγ ＋ cisplatin ＋ TRAIL group, and IFNγ ＋ etoposide ＋ TRAIL group. Conclusions IFNγ could sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing effect of TRAIL on SH-SY5Y cells.展开更多
The clinical characteristics of undifferentiated(embryonal) sarcoma of the liver(UESL) were investigated and the best treatment modalities were recommended.Both histology and immuno-histochemistry demonstrated the cel...The clinical characteristics of undifferentiated(embryonal) sarcoma of the liver(UESL) were investigated and the best treatment modalities were recommended.Both histology and immuno-histochemistry demonstrated the cellular features of this peculiar tumor.The tumor size was 12 cm × 9 cm × 8 cm in the right liver lobe.The patient underwent surgical resection of the tumor.The postoperative recovery was uneventful and she died eight months after diagnosis.The tumor showed mixed spindle and polygonal cells within the myxoid matrix.Some tumor cells contained eosinophilic hyaline globules that were positive for resistant diastase.Immunohistochemistry showed positive vimentin.Stellate and spindle cells were positively stained with alpha-1-antichymotrypsin(AACT) and CD68.This case indicates that UESL is not obviously differentiated in old-aged adults.展开更多
The clinical nursing specialist(CNS)is an expert who applies an expanded range of practical,theoretical,and research-based competencies to the care of patients within in a specialty clinical area within the larger dis...The clinical nursing specialist(CNS)is an expert who applies an expanded range of practical,theoretical,and research-based competencies to the care of patients within in a specialty clinical area within the larger discipline of nursing.A large number of studies consistently conclude that the CNS is a valuable healthcare resource that provides highquality clinical and evidence-based nursing practice and improves patient outcome.The CNS has been involved in healthcare practices for many years,with an increasingly diverse role.However,the training for the CNS in China is only in a preliminary developmental stage.The aim of this article is to review the history and development of the CNS role.Furthermore,the epidemiologic status of osteoporosis,as well as the feasibility and necessity of developing training programs in China for the osteoporosis CNS,will be discussed.展开更多
We acclimated adults of two viviparous （Phrynocephalus guinanens＆ and P. vlangalii） and one oviparous （P. versicolor） species of toad-headed lizards （Agamidae） to 28 ℃, 33 ℃ and 38 ℃ to examine whether therm...We acclimated adults of two viviparous （Phrynocephalus guinanens＆ and P. vlangalii） and one oviparous （P. versicolor） species of toad-headed lizards （Agamidae） to 28 ℃, 33 ℃ and 38 ℃ to examine whether thermal preference （preferred body temperature, Tp） and thermal tolerance （critical thermal minimum, CTMin; critical thermal maximum, CTMax） were affected by acclimation temperature, and correlate with body size and habitat use. Both Tp and CTMax were highest in P. versicolor and lowest in P. vlangalii, with P. guinanensis in between. The two viviparous species did not differ in CTMin and thermal tolerance range, and they both were more resistant to low temperatures and had a wider range of thermal tolerance than the oviparous species. Both CTMin and CTMax shifted upward as acclimation temperature increased in all the three species. Tp was higher in the lizards acclimated to 33 ℃ than in those to 28 ℃ or 38 ℃. The range of thermal tolerance was wider in the lizards acclimated to 28 ℃ than in those to 33 ℃ or 38 ℃. The data showed that： 1） thermal preference and tolerance were affected by acclimation temperature, and differed among the three species of Phrynocephalus lizards with different body sizes and habitat uses; 2） both Tp and CTMax were higher in the species exchanging heat more rapidly with the environment, and CTMin was higher in the species using warmer habitats during the active season; and 3） thermal preference and tolerance might correlat with body size and habitat use in Phrynocephalus lizards.展开更多
Objective:There are many reports on associations between spermatogenesis and partial azoospermia factor c(AZFc) deletions as well as duplications;however,results are conflicting,possibly due to differences in methodol...Objective:There are many reports on associations between spermatogenesis and partial azoospermia factor c(AZFc) deletions as well as duplications;however,results are conflicting,possibly due to differences in methodology and ethnic background.The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population,residents within Yunnan Province,ChinaMethods:A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population.The study was performed by sequence-tagged site plus/minus(STS+/) analysis followed by gene dosage and gene copy definition analysis.Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome(Y-SNP) multiplex assays based on single base primer extension technology.Results:The distribution of Y haplotypes was not significantly different between the case and control groups.The frequencies of both gr/gr(7.6% vs.8.5%) and b2/b3(6.3% vs.8.5%) deletions do not show significant differences.Similarly,single nucleotide variant(SNV) analysis shows no significant difference of gene copy definition between the cases and controls.However,the frequency of partial duplications in the infertile group(4.0%) is significantly higher than that in the control group(0.7%).Further,we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes.Conclusions:Our results show that male infertility is associated with partial AZFc duplications,but neither gr/gr nor b2/b3 deletions,suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.展开更多
To promote the utilization of renewable energy,such as photovoltaics,this paper proposes an optimal flexibility dispatch method for demand-side resources(DSR)based on the Stackelberg game theory.First,the concept of t...To promote the utilization of renewable energy,such as photovoltaics,this paper proposes an optimal flexibility dispatch method for demand-side resources(DSR)based on the Stackelberg game theory.First,the concept of the generalized DSR is analyzed and flexibility models for various DSR are constructed.Second,owing to the characteristics of small capacity but large-scale,an outer approximation is proposed to describe the aggregate flexibility of DSR.Then,the optimal flexibility dispatch model of DSR based on the Stackelberg game is established and a decentralized solution algorithm is designed to obtain the Stackelberg equilibrium.Finally,the actual data are utilized for the case study and the results show that,compared to the traditional centralized optimization method,the proposed optimal flexibility dispatch method can not only reduce the net load variability of the DSR aggregator but is beneficial for all DSR owners,which is more suitable for practical applications.展开更多
Lightweight infrared stealth and absorption-dominant electromagnetic interference(EMI)shielding materials are highly desirable in areas of aerospace,weapons,military and wearable electronics.Herein,lightweight and hig...Lightweight infrared stealth and absorption-dominant electromagnetic interference(EMI)shielding materials are highly desirable in areas of aerospace,weapons,military and wearable electronics.Herein,lightweight and high-efficiency dual-functional segregated nanocomposite foams with microcellular structures are developed for integrated infrared stealth and absorption-dominant EMI shielding via the efficient and scalable supercritical CO_(2)(SC-CO_(2))foaming combined with hydrogen bonding assembly and compression molding strategy.The obtained lightweight segregated nanocomposite foams exhibit superior infrared stealth performances benefitting from the synergistic effect of highly effective thermal insulation and low infrared emissivity,and outstanding absorption-dominant EMI shielding performances attributed to the synchronous construction of microcellular structures and segregated structures.Particularly,the segregated nanocomposite foams present a large radiation temperature reduction of 70.2℃ at the object temperature of 100℃,and a significantly improved EM wave absorptivity/reflectivity(A/R)ratio of 2.15 at an ultralow Ti_(3)C_(2)T_(x) content of 1.7 vol%.Moreover,the segregated nanocomposite foams exhibit outstanding working reliability and stability upon dynamic compression cycles.The results demonstrate that the lightweight and high-efficiency dual-functional segregated nanocomposite foams have excellent potentials for infrared stealth and absorption-dominant EMI shielding applications in aerospace,weapons,military and wearable electronics.展开更多
We maintained gravid Chinese skinks(Plestiodon chinensis) at three constant temperatures(25, 28 and 31 °C) during gestation, and randomly assigned eggs from each female to one of the same three temperatures for i...We maintained gravid Chinese skinks(Plestiodon chinensis) at three constant temperatures(25, 28 and 31 °C) during gestation, and randomly assigned eggs from each female to one of the same three temperatures for incubation to determine maternal thermal effects on female reproduction and hatchling phenotype. Maternal temperature affected egg-laying date, hatching success and hatchling linear size(snout-vent length, SVL) but not clutch size, egg size, egg component, and embryonic stage at laying. More specifically, females at higher temperatures laid eggs earlier than did those at low temperatures, eggs laid at 31 °C were less likely to hatch than those laid at 25 °C or 28 °C, and hatchlings from eggs laid at 31 °C were smaller in SVL. Our finding that maternal temperature(pre-ovipositional thermal condition) rather than incubation temperature(post-ovipositional thermal condition) affected hatching success indicated that embryos at early stages were more vulnerable to temperature than those at late stages. Our data provide an inference that moderate maternal temperatures enhance reproductive fitness in P. chinensis.展开更多
Cross-linked enzyme aggregates(CLEAs) of nitrile hydratase(NHase) ES-NHT-118 from Escherichia coli were prepared by using ammonium sulfate as precipitating agent followed by cross-linking with dextran polyaldehyde for...Cross-linked enzyme aggregates(CLEAs) of nitrile hydratase(NHase) ES-NHT-118 from Escherichia coli were prepared by using ammonium sulfate as precipitating agent followed by cross-linking with dextran polyaldehyde for the first time. In this process, egg white was added as protein feeder for facilitating the formation of CLEAs. The optimal conditions of the immobilization process were determined. Michaelis constants(Km) of free NHase and NHase CLEAs were also determined. The NHase CLEAs exhibited increased stability at varied pH and temperature conditions compared to its free counterpart. When exposed to high concentrations of acrylamide, NHase CLEAs also exhibited effective catalytic activity.展开更多
Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of...Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of primary resistance is not well understood.The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs;real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines.ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib.Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells.Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.展开更多
A novel three-dimensional hierarchical WO_(3)photoelectrode was prepared by solvothermal method,and ZnO was deposited on its surface by electrochemical method.The WO_(3)/ZnWO_(4)/ZnO multiphaseheterojunction photoelec...A novel three-dimensional hierarchical WO_(3)photoelectrode was prepared by solvothermal method,and ZnO was deposited on its surface by electrochemical method.The WO_(3)/ZnWO_(4)/ZnO multiphaseheterojunction photoelectrode was prepared by further annealing treatment to explore the photoinduced cathodic protection(CP)performance.Compared with WO_(3)and ZnO,the photoinduced CP and electron storage capacity performance of WO_(3)/ZnWO_(4)/ZnO is significantly improved in 3.5%NaCl solution without adding any hole scavenger.The electron storage capacity of the WO_(3)/ZnWO_(4)/ZnO heterojunction makes it possible to continuously protect metallic materials in the dark after switching off the light,which can realize long-term and effective photoinduced CP.展开更多
Black hole mass is one of the fundamental physical parameters of active galactic nuclei （AGNs）, for which many methods of estimation have been proposed. One set of methods assumes that the broad-line region （BLR） ...Black hole mass is one of the fundamental physical parameters of active galactic nuclei （AGNs）, for which many methods of estimation have been proposed. One set of methods assumes that the broad-line region （BLR） is gravitationally bound by the central black hole potential, so the black hole mass can be estimated from the orbital radius and the Doppler velocity. Another set of methods assumes the observed variability timescale is determined by the orbital timescale near the innermost stable orbit around the Schwarzschild black hole or the Kerr black hole, or by the characteristic timescale of the accretion disk. We collect a sample of 21 AGNs, for which the minimum variability timescales have been obtained and their black hole masses （Mσ） have been well estimated from the stellar velocity dispersion or the BLR size-luminosity relation. Using the minimum variability timescales we estimated the black hole masses for 21 objects by the three different methods, the results are denoted by Ms, Mk and Md,respectively. We compared each of them with Mσ individually and found that： （1） using the minimum variability timescale with the Kerr black hole theory leads to small differences between Mσ and Mk, none exceeding one order of magnitude, and the mean difference between them is about 0.53 dex; （2） using the minimum variability timescale with the Schwarzschild black hole theory leads to somewhat larger difference between Mσ and Ms： larger than one order of magnitude for 6 of the 21 sources, and the mean difference is 0.74 dex; （3） using the minimum variability timescale with the accretion disk theory leads to much larger differences between Mσ and Md, for 13 of the 21 sources the differences are larger than two orders of magnitude; and the mean difference is as high as about 2.01 dex.展开更多
Objective To explore themechanism of Sangbaipi Decoction(SBPD)in the treatment of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD).Methods The active compounds of SBPD and targets of those active c...Objective To explore themechanism of Sangbaipi Decoction(SBPD)in the treatment of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD).Methods The active compounds of SBPD and targets of those active compounds were collectedfrom the TCMSP database.Then we built the AECOPD target database by OMIM,GeneCards,PharmGKB and DrugBank.The intersectional targets arethep-otentialtargets of SBPD in the treatment ofAECOPD.We built"Potential Active Compounds-Drug-AECOPDTargets"Network via Cytoscape software.Weconstruct the Protein-Protein Inter-action(PPI)network through STRING database.We analyze the PPI network and“Potential Active Compounds-Drug-AECOPD Targets”Network via CytoNCA,then we got the core targets and key active compounds of SBPDin the treatment ofAE-COPD.TheGeneOntology(GO)function enrichment and KEGG pathway enrichment on the intersection targets were analyzed by R software.The key active compounds is molecularly docked with the core target protein receptors through AutoDock Vina soft-ware,and the 2D ligand-protein interaction diagramsare drawn through LigPlot 2.2 software.ResultsThere were 109 active compounds,205 targets of SBPD.2837 targetsrelated to AECOPD were picked out.157 intersectional targets were obtained from the two datas.We get 3 coretargets(TP53,JUN,VEGFA)and five key active compounds(quercetin,luteolin,kaempferol,wogonin,arachidonic acid)of SBPD.The GO function enrichment analysis showed that 2552 entries(P<0.05),of which there were 2261 biological processes(BP)items,and 84 related items of cell composition(CC),and 207 molecular function(MF)items.KEGG pathway enrichment analysis showed that 167 signaling path-ways(P<0.05),mainly including IL 17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway.The molecular dock-ing structure shows that the key active compounds of SBPD have good affinities with the core targets.ConclusionSBPD may treatAECOPD by anti-inflammatory,anti-oxidation,airway mucus secretion reduction,and pulmonary vascular remodeling reduction.展开更多
Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigid...Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.展开更多
BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive...BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.展开更多
基金financially supported by the National Key Research and Development Project of the Ministry of Science and Technology of China(No.2022YFB4601000)the Fundamental Research Funds for the Central Universities(No.2042023kf0103)the Ministry of Trade,Industry and Energy,Korea(No.20013095)。
文摘The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the columnar structures and fine martensite formation.This study investigated the effect of carbon nanotubes(CNTs)addition on the microstructure and mechanical properties of grade 1 CP-Ti(Gr-1)during the laser powder bed fusion(L-PBF)process.A minute amount of 0.2%mass fraction(wt%)CNTs addition resulted in a high yield strength of approximately 700 MPa and exceptional ductility of 25.7%.Therein,a portion of the CNTs dissolved in the matrix as solute atoms,contributing to solution strengthening,while others were transformed into Ti C_(x)through an in situ reaction with the Ti matrix.Furthermore,the addition of CNTs resulted in the formation of a larger fraction of equiaxed grains and increased the activity of basal and prismatic slip systems.Hence,Gr-1 with CNTs exhibited significantly increased ductility while maintaining a high strength comparable to that of Gr-1 without CNTs.The insights gained from this study provide a novel approach for designing strong and ductile Ti alloys for AM.
基金supported by the 2023 training program for discipline leaders in natural science and engineering technology of Qinghai province-“Kunlun Talents·Science and Technology leaders.”。
文摘Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix remodeling.Although KBD and OA share overlapping clinical and pathological features,key differences exist in their etiology and disease progression.KBD preferentially affects children aged 3-12 years,whereas OA predominantly affects older individuals between the age of 40-60 years.KBD cartilage necrosis originates in the deep layers of the epiphyseal plate and articular cartilage,progressing toward the cartilage surface.In contrast,OA cartilage destruction initiates at the articular cartilage surface and gradually progresses to expose the subchondral bone[1,2].
文摘BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditionally,the primary treatment has been laparoscopic appendectomy(LA).CASE SUMMARY A 63-year-old female presented with changes in bowel habits.Colonoscopy revealed an ileocecal LST.The patient underwent endoscopic submucosal dissection.Postoperative follow-up colonoscopy revealed mucosal elevation at the appendiceal orifice,with pathology confirming tubular adenoma.Abdominal computed tomography indicated a suspicious appendiceal tumor,leading to LA with partial cecectomy.The postoperative recovery was uneventful.At the 1-year follow-up,colonoscopy revealed no evidence of tumor recurrence.CONCLUSION Ileocecal LSTs with appendiceal tubular adenomas are traditionally treated with LA.endoscopic submucosal dissection can also yield favorable outcomes.
基金supported by the Fund of Key Laboratory of Biomedical Engineering of Hainan Province(No.BME20240001)the STI2030-Major Projects(No.2021ZD0200104)the National Natural Science Foundations of China under Grant 61771437.
文摘Deep learning networks are increasingly exploited in the field of neuronal soma segmentation.However,annotating dataset is also an expensive and time-consuming task.Unsupervised domain adaptation is an effective method to mitigate the problem,which is able to learn an adaptive segmentation model by transferring knowledge from a rich-labeled source domain.In this paper,we propose a multi-level distribution alignment-based unsupervised domain adaptation network(MDA-Net)for segmentation of 3D neuronal soma images.Distribution alignment is performed in both feature space and output space.In the feature space,features from different scales are adaptively fused to enhance the feature extraction capability for small target somata and con-strained to be domain invariant by adversarial adaptation strategy.In the output space,local discrepancy maps that can reveal the spatial structures of somata are constructed on the predicted segmentation results.Then thedistribution alignment is performed on the local discrepancies maps across domains to obtain a superior discrepancy map in the target domain,achieving refined segmentation performance of neuronal somata.Additionally,after a period of distribution align-ment procedure,a portion of target samples with high confident pseudo-labels are selected as training data,which assist in learning a more adaptive segmentation network.We verified the superiority of the proposed algorithm by comparing several domain adaptation networks on two 3D mouse brain neuronal somata datasets and one macaque brain neuronal soma dataset.
基金supported by funds from the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education MinistryNational Nature Science Fund, Support Grant 81301932+2 种基金the grants from the University Cancer Foundation via the Sister Institution Network Fund at The University of Texas MD Anderson Cancer Center and, in part, by the National Institutes of Health through MD Anderson Cancer Center Support Grant (CA016672)as some of these studies were performed in the North Campus Flow Cytometry and Cellular Imaging Core (PI: Ronald A. De Pinho, MD)supported by the grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, China
文摘Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.
基金the National Natural Sciences Foundation of China(39470739)the Ministry of Public Health Research Foundation(20122167)the Doctor Startup-Natural Science Foundation of Li-aoning Province (20041047)
文摘Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible molecular mechanisms. Methods The expressions of Caspase 8 mRNA and protein were detected with RT-PCR and Western blot analysis. The effects of IFNγ, TRAIL, IFNγ ＋ TRAIL, IFNγ ＋ Caspase 8 inhibitor ＋ TRAIL, IFNγ ＋ cisplatin ＋ TRAIL, and IFNγ ＋ etoposide ＋ TRAIL on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. The relative Caspase 8 activity was measured with colorimetric assay. Results Caspase 8 was undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and protein was found after treatment with IFNγ. SH-SY5Y ceils themselves were not sensitive to TRAIL, but those expressing Caspase 8 after treatment with IFNγ were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8 was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y cells in IFNγ ＋ TRAIL group was significantly higher than those of control group, IFNγ group, TRAIL group, and inhibitor group （ P 〈 0. 01 ）. There was no significant difference among IFNγ ＋ TRAIL group, IFNγ ＋ cisplatin ＋ TRAIL group, and IFNγ ＋ etoposide ＋ TRAIL group. Conclusions IFNγ could sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing effect of TRAIL on SH-SY5Y cells.
基金Supported by The Key Oncologic Subject Foundation of Hebei Province (No.200552),China
文摘The clinical characteristics of undifferentiated(embryonal) sarcoma of the liver(UESL) were investigated and the best treatment modalities were recommended.Both histology and immuno-histochemistry demonstrated the cellular features of this peculiar tumor.The tumor size was 12 cm × 9 cm × 8 cm in the right liver lobe.The patient underwent surgical resection of the tumor.The postoperative recovery was uneventful and she died eight months after diagnosis.The tumor showed mixed spindle and polygonal cells within the myxoid matrix.Some tumor cells contained eosinophilic hyaline globules that were positive for resistant diastase.Immunohistochemistry showed positive vimentin.Stellate and spindle cells were positively stained with alpha-1-antichymotrypsin(AACT) and CD68.This case indicates that UESL is not obviously differentiated in old-aged adults.
基金The work was supported by the Comprehensive investment strategic emerging industries related construction projects in“twelfth five-year”for Tianjin(Tianjin Education Committee[2011]no.61).
文摘The clinical nursing specialist(CNS)is an expert who applies an expanded range of practical,theoretical,and research-based competencies to the care of patients within in a specialty clinical area within the larger discipline of nursing.A large number of studies consistently conclude that the CNS is a valuable healthcare resource that provides highquality clinical and evidence-based nursing practice and improves patient outcome.The CNS has been involved in healthcare practices for many years,with an increasingly diverse role.However,the training for the CNS in China is only in a preliminary developmental stage.The aim of this article is to review the history and development of the CNS role.Furthermore,the epidemiologic status of osteoporosis,as well as the feasibility and necessity of developing training programs in China for the osteoporosis CNS,will be discussed.
基金supported by the grants from the National Natural Science Foundation of China(31071910 and 31200282)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘We acclimated adults of two viviparous （Phrynocephalus guinanens＆ and P. vlangalii） and one oviparous （P. versicolor） species of toad-headed lizards （Agamidae） to 28 ℃, 33 ℃ and 38 ℃ to examine whether thermal preference （preferred body temperature, Tp） and thermal tolerance （critical thermal minimum, CTMin; critical thermal maximum, CTMax） were affected by acclimation temperature, and correlate with body size and habitat use. Both Tp and CTMax were highest in P. versicolor and lowest in P. vlangalii, with P. guinanensis in between. The two viviparous species did not differ in CTMin and thermal tolerance range, and they both were more resistant to low temperatures and had a wider range of thermal tolerance than the oviparous species. Both CTMin and CTMax shifted upward as acclimation temperature increased in all the three species. Tp was higher in the lizards acclimated to 33 ℃ than in those to 28 ℃ or 38 ℃. The range of thermal tolerance was wider in the lizards acclimated to 28 ℃ than in those to 33 ℃ or 38 ℃. The data showed that： 1） thermal preference and tolerance were affected by acclimation temperature, and differed among the three species of Phrynocephalus lizards with different body sizes and habitat uses; 2） both Tp and CTMax were higher in the species exchanging heat more rapidly with the environment, and CTMin was higher in the species using warmer habitats during the active season; and 3） thermal preference and tolerance might correlat with body size and habitat use in Phrynocephalus lizards.
基金Project(No.GREKF09-08)supported by the State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,China
文摘Objective:There are many reports on associations between spermatogenesis and partial azoospermia factor c(AZFc) deletions as well as duplications;however,results are conflicting,possibly due to differences in methodology and ethnic background.The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population,residents within Yunnan Province,ChinaMethods:A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population.The study was performed by sequence-tagged site plus/minus(STS+/) analysis followed by gene dosage and gene copy definition analysis.Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome(Y-SNP) multiplex assays based on single base primer extension technology.Results:The distribution of Y haplotypes was not significantly different between the case and control groups.The frequencies of both gr/gr(7.6% vs.8.5%) and b2/b3(6.3% vs.8.5%) deletions do not show significant differences.Similarly,single nucleotide variant(SNV) analysis shows no significant difference of gene copy definition between the cases and controls.However,the frequency of partial duplications in the infertile group(4.0%) is significantly higher than that in the control group(0.7%).Further,we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes.Conclusions:Our results show that male infertility is associated with partial AZFc duplications,but neither gr/gr nor b2/b3 deletions,suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.
基金supported by Science and Technology Project of State Grid Hebei Electric Power Company(SGHE0000DKJS2000228)
文摘To promote the utilization of renewable energy,such as photovoltaics,this paper proposes an optimal flexibility dispatch method for demand-side resources(DSR)based on the Stackelberg game theory.First,the concept of the generalized DSR is analyzed and flexibility models for various DSR are constructed.Second,owing to the characteristics of small capacity but large-scale,an outer approximation is proposed to describe the aggregate flexibility of DSR.Then,the optimal flexibility dispatch model of DSR based on the Stackelberg game is established and a decentralized solution algorithm is designed to obtain the Stackelberg equilibrium.Finally,the actual data are utilized for the case study and the results show that,compared to the traditional centralized optimization method,the proposed optimal flexibility dispatch method can not only reduce the net load variability of the DSR aggregator but is beneficial for all DSR owners,which is more suitable for practical applications.
基金the National Natural Science Foundation of China (52273083, 51903145)Key Research and Development Project of Shaanxi Province (2023-YBGY-476)+1 种基金Natural Science Foundation of Chongqing,China (CSTB2023NSCQ-MSX0691)National College Students Innovation and Entrepreneurship Training Program (202310699172)
文摘Lightweight infrared stealth and absorption-dominant electromagnetic interference(EMI)shielding materials are highly desirable in areas of aerospace,weapons,military and wearable electronics.Herein,lightweight and high-efficiency dual-functional segregated nanocomposite foams with microcellular structures are developed for integrated infrared stealth and absorption-dominant EMI shielding via the efficient and scalable supercritical CO_(2)(SC-CO_(2))foaming combined with hydrogen bonding assembly and compression molding strategy.The obtained lightweight segregated nanocomposite foams exhibit superior infrared stealth performances benefitting from the synergistic effect of highly effective thermal insulation and low infrared emissivity,and outstanding absorption-dominant EMI shielding performances attributed to the synchronous construction of microcellular structures and segregated structures.Particularly,the segregated nanocomposite foams present a large radiation temperature reduction of 70.2℃ at the object temperature of 100℃,and a significantly improved EM wave absorptivity/reflectivity(A/R)ratio of 2.15 at an ultralow Ti_(3)C_(2)T_(x) content of 1.7 vol%.Moreover,the segregated nanocomposite foams exhibit outstanding working reliability and stability upon dynamic compression cycles.The results demonstrate that the lightweight and high-efficiency dual-functional segregated nanocomposite foams have excellent potentials for infrared stealth and absorption-dominant EMI shielding applications in aerospace,weapons,military and wearable electronics.
基金the National Science Foundation of China (31670399 and 31670422)
文摘We maintained gravid Chinese skinks(Plestiodon chinensis) at three constant temperatures(25, 28 and 31 °C) during gestation, and randomly assigned eggs from each female to one of the same three temperatures for incubation to determine maternal thermal effects on female reproduction and hatchling phenotype. Maternal temperature affected egg-laying date, hatching success and hatchling linear size(snout-vent length, SVL) but not clutch size, egg size, egg component, and embryonic stage at laying. More specifically, females at higher temperatures laid eggs earlier than did those at low temperatures, eggs laid at 31 °C were less likely to hatch than those laid at 25 °C or 28 °C, and hatchlings from eggs laid at 31 °C were smaller in SVL. Our finding that maternal temperature(pre-ovipositional thermal condition) rather than incubation temperature(post-ovipositional thermal condition) affected hatching success indicated that embryos at early stages were more vulnerable to temperature than those at late stages. Our data provide an inference that moderate maternal temperatures enhance reproductive fitness in P. chinensis.
基金Supported by the National Nature Science Foundation of China(Nos.21306039,21276060,21276062)the Natural Science Foundation of Hebei Province(B2015202082,B2016202027)the Tianjin City High School Science&Technology Fund Planning Project(20140513)
文摘Cross-linked enzyme aggregates(CLEAs) of nitrile hydratase(NHase) ES-NHT-118 from Escherichia coli were prepared by using ammonium sulfate as precipitating agent followed by cross-linking with dextran polyaldehyde for the first time. In this process, egg white was added as protein feeder for facilitating the formation of CLEAs. The optimal conditions of the immobilization process were determined. Michaelis constants(Km) of free NHase and NHase CLEAs were also determined. The NHase CLEAs exhibited increased stability at varied pH and temperature conditions compared to its free counterpart. When exposed to high concentrations of acrylamide, NHase CLEAs also exhibited effective catalytic activity.
基金supported by National Basic Research Program of China (Grant No.2015CB964903)Natural Science Foundation of Tianjin (Grant No.15JCQNJC44800 and 18JCQNJC81300)+3 种基金National Natural Science Foundation of China (Grant No.81702481, 81701224, 81802873 and 81600083)CAMS Innovation Fund for Medical Sciences (Grant No.201612M-1-003 2017-12M-1-015)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No.2017PT31033, 2018RC31002, 2018PT32034)
文摘Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of primary resistance is not well understood.The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs;real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines.ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib.Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells.Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.
基金financially supported by the National Natural Science Foundation of China(No.41976036)the State Key Laboratory for Marine Corrosion and Protection,Luoyang Ship Material Research Institute(LSMRI)(Nos.KF190408 and KF190404)。
文摘A novel three-dimensional hierarchical WO_(3)photoelectrode was prepared by solvothermal method,and ZnO was deposited on its surface by electrochemical method.The WO_(3)/ZnWO_(4)/ZnO multiphaseheterojunction photoelectrode was prepared by further annealing treatment to explore the photoinduced cathodic protection(CP)performance.Compared with WO_(3)and ZnO,the photoinduced CP and electron storage capacity performance of WO_(3)/ZnWO_(4)/ZnO is significantly improved in 3.5%NaCl solution without adding any hole scavenger.The electron storage capacity of the WO_(3)/ZnWO_(4)/ZnO heterojunction makes it possible to continuously protect metallic materials in the dark after switching off the light,which can realize long-term and effective photoinduced CP.
基金Supported by the National Natural Science Foundation of China.
文摘Black hole mass is one of the fundamental physical parameters of active galactic nuclei （AGNs）, for which many methods of estimation have been proposed. One set of methods assumes that the broad-line region （BLR） is gravitationally bound by the central black hole potential, so the black hole mass can be estimated from the orbital radius and the Doppler velocity. Another set of methods assumes the observed variability timescale is determined by the orbital timescale near the innermost stable orbit around the Schwarzschild black hole or the Kerr black hole, or by the characteristic timescale of the accretion disk. We collect a sample of 21 AGNs, for which the minimum variability timescales have been obtained and their black hole masses （Mσ） have been well estimated from the stellar velocity dispersion or the BLR size-luminosity relation. Using the minimum variability timescales we estimated the black hole masses for 21 objects by the three different methods, the results are denoted by Ms, Mk and Md,respectively. We compared each of them with Mσ individually and found that： （1） using the minimum variability timescale with the Kerr black hole theory leads to small differences between Mσ and Mk, none exceeding one order of magnitude, and the mean difference between them is about 0.53 dex; （2） using the minimum variability timescale with the Schwarzschild black hole theory leads to somewhat larger difference between Mσ and Ms： larger than one order of magnitude for 6 of the 21 sources, and the mean difference is 0.74 dex; （3） using the minimum variability timescale with the accretion disk theory leads to much larger differences between Mσ and Md, for 13 of the 21 sources the differences are larger than two orders of magnitude; and the mean difference is as high as about 2.01 dex.
文摘Objective To explore themechanism of Sangbaipi Decoction(SBPD)in the treatment of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD).Methods The active compounds of SBPD and targets of those active compounds were collectedfrom the TCMSP database.Then we built the AECOPD target database by OMIM,GeneCards,PharmGKB and DrugBank.The intersectional targets arethep-otentialtargets of SBPD in the treatment ofAECOPD.We built"Potential Active Compounds-Drug-AECOPDTargets"Network via Cytoscape software.Weconstruct the Protein-Protein Inter-action(PPI)network through STRING database.We analyze the PPI network and“Potential Active Compounds-Drug-AECOPD Targets”Network via CytoNCA,then we got the core targets and key active compounds of SBPDin the treatment ofAE-COPD.TheGeneOntology(GO)function enrichment and KEGG pathway enrichment on the intersection targets were analyzed by R software.The key active compounds is molecularly docked with the core target protein receptors through AutoDock Vina soft-ware,and the 2D ligand-protein interaction diagramsare drawn through LigPlot 2.2 software.ResultsThere were 109 active compounds,205 targets of SBPD.2837 targetsrelated to AECOPD were picked out.157 intersectional targets were obtained from the two datas.We get 3 coretargets(TP53,JUN,VEGFA)and five key active compounds(quercetin,luteolin,kaempferol,wogonin,arachidonic acid)of SBPD.The GO function enrichment analysis showed that 2552 entries(P<0.05),of which there were 2261 biological processes(BP)items,and 84 related items of cell composition(CC),and 207 molecular function(MF)items.KEGG pathway enrichment analysis showed that 167 signaling path-ways(P<0.05),mainly including IL 17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway.The molecular dock-ing structure shows that the key active compounds of SBPD have good affinities with the core targets.ConclusionSBPD may treatAECOPD by anti-inflammatory,anti-oxidation,airway mucus secretion reduction,and pulmonary vascular remodeling reduction.
文摘Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.
基金Supported by China Scientific Research Fund for HER2 Target from China Anti-Cancer Association,No.CORP-239-M9.
文摘BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.
