Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

Exploring the sensitivity of α-decay half-life to neutron skin thickness for nuclei around ^(208)Pb

Based on the newest experimentally extracted nuclear density distributions for double-magic nucleus208Pb(Tarbert et al. in Phys Rev Lett 112:242502, 2014),the sensitivity of α-decay half-life to nuclear skin thickness is explored in the vicinity of the shell closure region around208 Pb, i.e., isotopes of Z ? 82 and isotones of N ? 126.With the two-parameter Fermi(2PF) density distributions and an analytically derived formula, the α-decay half-life is found to be closely related to the magnitude of nuclear skin thickness. For a decays to the Z ? 82 isotopes, the α-decay half-life is found to decrease with the increasing neutron skin thickness, while the opposite behavior is found for a decays to the N ? 126 isotones. Therefore, it could be a possible way to extract the nuclear skin thickness from measured α-decay half-lives.

Antibody fragments: Prolonging circulation half-life special issue-antibody research

Antibodies are currently the fastest growing class of therapeutic proteins. When antibody fragments are included, there are over thirty-five antibody-based medicines approved for human therapy. Many more antibody and antibody-like fragments are being evaluated clinically. Production of antibody fragments can be efficient and their compact size can allows for better tissue extravasation into solid tumors than full antibodies. Unfortunately, a key limitation of antibody fragments for systemic use is their short half-life in circulation. Prolonging their circulation half-life can be accomplished clinically by the covalent conjugation of the antibody fragment to the water-soluble polymer, poly(ethylene glycol) (PEG). Many polymers and strategies are also being pursued to increase antibody fragment half-life.

鼻咽癌中Period2下调ERK/MAPK磷酸化水平的机制

目的探讨生物钟基因Period2在鼻咽癌中下调ERK/MAPK磷酸化水平的分子机制。方法用慢病毒对细胞进行感染,构建细胞系。采用Label-free蛋白质组学检测方法对PER2蛋白表达进行验证。采用不同浓度的ERK通路激活剂Ceramide C6干预各组细胞,MTT检测各组细胞的增殖能力,筛选最佳药物浓度和作用时间。采用ERK通路激活剂Ceramide C6干预细胞,正常对照组采用等剂量药物溶剂进行处理,分为6组。Western blot检测各组细胞PER2、ERK、p38MAPK、p-ERK、p-p38MAPK蛋白的表达。流式细胞术检测细胞周期,Transwell实验检测各组细胞侵袭能力,进一步明确PER2调控ERK、MAPK磷酸化的机制。用免疫组化检测PER2、p-ERK在人体鼻咽癌样本中的表达,并分析PER2、p-ERK与鼻咽癌临床特点的相关性。结果蛋白质组学检测结果示PER2过表达组的PER2蛋白表达明显高于阴性病毒对照组和空白对照组(P<0.05)。Top 20差异蛋白显示MAPK3在PER2过表达组和对照组差异有统计学意义(P<0.05)。MTT实验结果:不同药物浓度处理后,根据每组细胞抑制率,得出最佳的药物作用浓度10μmol/L,最佳处理时间24 h。WB结果显示PER2过表达下调p-ERK、p-p38MAPK蛋白表达,ERK通路激活剂Ceramide C6干预后,在PER2-OE组中ERK、p38MAPK蛋白水平无明显变化,但p-ERK、p-p38MAPK蛋白表达水平上调,干预前后差异有统计学意义(P<0.01)。细胞周期实验结果显示:ERK通路激活剂Ceramide C6干预各组细胞后,使细胞在G1期的比例明显增加,而在G2期数量减少。Transwell实验结果显示PER2过表达抑制细胞侵袭能力,此种现象不能被磷酸激酶逆转。在鼻咽癌组织、鼻咽部黏膜中PER2蛋白、p-ERK蛋白表达阳性率差异有统计学意义(P<0.05)。PER2蛋白表达与肿瘤的T分期相关(P<0.05)。在鼻咽癌组织中PER2蛋白与p-ERK蛋白表达相关(P<0.05)。结论PER2过表达下调ERK/MAPK磷酸化水平,可能不是直接作用于ERK和p38MAPK的磷酸化位点,而是与调控ERK和p38MAPK的关键节点有关。鼻咽癌组织中PER2蛋白呈低表达,p-ERK蛋白呈高表达,两者相关,并且与肿瘤的发生、发展关系密切。

Determinations of ^(171)Er half-life and some ^(171)Tm transition energies

The neutrons have been captured by Erbium nuclei which were received by using clinical electron linear accelerator. In this experiment, the possibility of the neutron capture process has been observed because of emitted neutrons appearing in the experimental area. In particular,neutron capture of ^(170)Er nucleus has been observed. After the neutron capture of ^(170)Er nucleus, the unstable ^(171)Er has been formed and decayed into the ^(171)Tm. By using this reaction path, some transition energies of ^(171)Tm obtained from the residual activity measurements and the half-life of ^(171)Er have been determined, and they are in agreement with adopted values in the literature.

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

Improved systemic half-life of glucagon-like peptide-1-loaded carbonate apatite nanoparticles in rats

BACKGROUND Glucagon-like peptide-1(GLP1)is an endogenous peptide that regulates blood glucose level.But its susceptibility to rapid metabolic degradation limits its therapeutic use.AIM To prepare GLP1-encapsulated nanosize particle with controlled release property to improve the systemic half-life of GLP1.METHODS GLP1 nanoparticles were prepared by complexation of GLP1 with carbonate apatite nanoparticles(CA NPs).The physicochemical properties of the CA NPs,the effects of GLP1-loaded CA NPs on cell viability,and the systemic bioavailability of GLP1 after CA NPs administration were determined.RESULTS The GLP1-loaded CA NPs was within 200 nm in size and stable in fetal bovine serum.The formulation did not affect the viability of human cell lines suggesting that the accumulation of CA NPs in target tissues is safe.In Sprague Dawley rats,the plasma GLP1 Levels as measured from the GLP1-loaded CA NPs-treated rats,were significantly higher than that of the control rats and free GLP1-treated rats at 1 h post-treatment(P<0.05),and the level remained higher than the other two groups for at least 4 h.CONCLUSION The GLP1-loaded CA NPs improved the plasma half-life of GLP1.The systemic bioavailability of GLP1 is longer than other GLP1 nanoparticles reported to date.

Preweaning period is a critical window for rumen microbial regulation of average daily gain in Holstein heifer calves

Background Rumen bacterial groups can affect growth performance,such as average daily gain(ADG),feed intake,and efficiency.The study aimed to investigate the inter-relationship of rumen bacterial composition,rumen fermentation indicators,serum indicators,and growth performance of Holstein heifer calves with different ADG.Twelve calves were chosen from a trail with 60 calves and divided into higher ADG(HADG,high pre-and post-weaning ADG,n=6)and lower ADG(LADG,low pre-and post-weaning ADG,n=6)groups to investigate differences in bacterial composition and functions and host phenotype.Results During the preweaning period,the relative abundances of propionate producers,including g_norank_f_Butyricicoccaceae,g_Pyramidobacter,and g_norank_f_norank_o_Clostridia_vadin BB60_group,were higher in HADG calves(LDA>2,P<0.05).Enrichment of these bacteria resulted in increased levels of propionate,a gluconeogenic precursor,in preweaning HADG calves(adjusted P<0.05),which consequently raised serum glucose concentrations(adjusted P<0.05).In contrast,the relative abundances of rumen bacteria in post-weaning HADG calves did not exert this effect.Moreover,no significant differences were observed in rumen fermentation parameters and serum indices between the two groups.Conclusions The findings of this study revealed that the preweaning period is the window of opportunity for rumen bacteria to regulate the ADG of calves.

Ultrafast dynamics of femtosecond laser-induced high spatial frequency periodic structures on silicon surfaces

Femtosecond laser-induced periodic surface structures(LIPSS)have been extensively studied over the past few decades.In particular,the period and groove width of high-spatial-frequency LIPSS(HSFL)is much smaller than the diffraction limit,making it a useful method for efficient nanomanufacturing.However,compared with the low-spatial-frequency LIPSS(LSFL),the structure size of the HSFL is smaller,and it is more easily submerged.Therefore,the formation mechanism of HSFL is complex and has always been a research hotspot in this field.In this study,regular LSFL with a period of 760 nm was fabricated in advance on a silicon surface with two-beam interference using an 800 nm,50 fs femtosecond laser.The ultrafast dynamics of HSFL formation on the silicon surface of prefabricated LSFL under single femtosecond laser pulse irradiation were observed and analyzed for the first time using collinear pump-probe imaging method.In general,the evolution of the surface structure undergoes five sequential stages:the LSFL begins to split,becomes uniform HSFL,degenerates into an irregular LSFL,undergoes secondary splitting into a weakly uniform HSFL,and evolves into an irregular LSFL or is submerged.The results indicate that the local enhancement of the submerged nanocavity,or the nanoplasma,in the prefabricated LSFL ridge led to the splitting of the LSFL,and the thermodynamic effect drove the homogenization of the splitting LSFL,which evolved into HSFL.

2-9 Half-life Measurement of 94mRu44+ at CSRe

A radioactive nucleus is characterized with an intrinsic half-life. However, for a nuclear species, the half-lives inneutral atoms could be very different from that in highly charged ions. The half-lives of some highly charged ionshave been directly measured at GSI for multiple motivations[1]. In the same case, the nuclear state(i:e the isomer)may be in the range of several tens of microseconds and their half-live can be measured using isochronous massspectrometry. The J = 8+ isomeric state in 94Ru was chosen to test this method. The half-life of this isomer is71 s [2] in neutral atoms, and the excitation energy is 2.64 MeV. The internal conversion coefficient of this decayin neutral atom is 0.335. So its half-life in the bare nucleus would be modified to be 94.78 s when the internalconversion channel is blocked.

ON THE STABILITY OF PERIODIC SOLUTIONS OF PIECEWISE SMOOTH PERIODIC DIFFERENTIAL EQUATIONS

In this paper,we address the stability of periodic solutions of piecewise smooth periodic differential equations.By studying the Poincarémap,we give a sufficient condition to judge the stability of a periodic solution.We also present examples of some applications.

Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages phenotype.In a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

VR技术在游戏设计中的交互与特征研究——以游戏《Half-Life:Alyx》为例

游戏不光需要在剧情、美术设计上表现出彩,在游戏的可操作性内容设计上也同样需要有吸引力。通过VR游戏《Half-Life:Alyx》的体验可以了解到有着丰富游戏制作经验的大厂对VR游戏中交互设计内容的选择与理解,也可以学习到大厂对于游戏剧情语言的把握。

Tuning Second Chern Number in a Four-Dimensional Topological Insulator by High-Frequency Time-Periodic Driving

Floquet engineering has attracted considerable attention as a promising approach for tuning topological phase transitions.We investigate the effects of high-frequency time-periodic driving in a four-dimensional(4D)topological insulator,focusing on topological phase transitions at the off-resonant quasienergy gap.The 4D topological insulator hosts gapless three-dimensional boundary states,characterized by the second Chern number C_(2).We demonstrate that the second Chern number of 4D topological insulators can be modulated by tuning the amplitude of time-periodic driving.This includes transitions from a topological phase with C_(2)=±3 to another topological phase with C_(2)=±1,or to a topological phase with an even second Chern number C_(2)=±2,which is absent in the 4D static system.Finally,the approximation theory in the high-frequency limit further confirms the numerical conclusions.

Solitons and Their Biperiodic Pulsation in Ultrafast Fiber Lasers Based on CB/GO

The carbon black(CB)is introduced to manufacture CB/graphene oxide(GO)composite material to mitigate limitations of GO as a saturable absorber with the excellent performance in ultrafast fiber lasers.At a central wavelength of 1555.5 nm,the stable mode-locked pulse with width of 656 fs,repetition rate of 20.16 MHz,and high signal-to-noise ratio of 82.07 dB is experimentally obtained.Additionally,experimental observations for pulsation phenomena of vector biperiodic solitons combining period-1 and period-17,period-2 and period-32,period-3 and period-36 are verified via simulations.

Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Cranial ultrasound in perioperative period of acute severe traumatic brain injury

Objective To observe the value of cranial ultrasound for perioperative patients with acute severe traumatic brain injury(sTBI).Methods Data of 55 sTBI patients who underwent craniotomy were retrospectively analyzed.The patients were divided into observation group(n=15)and control group(n=40)according to received perioperative cranial ultrasound or not.The general data and surgical data were compared between groups,and ultrasonic data of observation group were analyzed.Results The proportions of good prognosis 1 and 6 months after operation in observation group were both higher than those in control group,while the incidence of cerebral infarction in observation group was lower than that in control group(all P<0.05).No significant difference of general data nor other surgical data was found between groups(all P>0.05).Acute encephalocele occurred in 1 case in observation group during operation,and cranial ultrasound accurately showed the contralateral secondary epidural hematoma.Increased intracranial pressure in different degrees were found in all 15 cases(15/15,100%)in observation group after operation with transcranial color coded Doppler(TCCD)or transcranial Doppler(TCD),while cerebral vascular spasm was observed in 5 cases(5/15,33.33%),among them 4 cases(4/5,80.00%)were diagnosed cerebral infarction based on CT examination.Conclusion Cranial ultrasound could be used to evaluate changes of sTBI in perioperative period and guide adjusting treatment strategy in time,being valuable for reducing risk of postoperative cerebral infarction and improving prognosis.

Interference-induced suppression of particle emission from a Bose-Einstein condensate in lattice with time-periodic modulations

Emission of matter-wave jets from a parametrically driven condensate has attracted significant experimental and theoretical attention due to the appealing visual effects and potential metrological applications.In this work,we investigate the collective particle emission from a Bose-Einstein condensate confined in a one-dimensional lattice with periodically modulated interparticle interactions.We give the regimes for discrete modes,and find that the emission can be distinctly suppressed.The configuration induces a broad band,but few particles are ejected due to the interference of the matter waves.We further qualitatively model the emission process and demonstrate the short-time behaviors.This engineering provides a way to manipulate the propagation of particles and the corresponding dynamics of condensates in lattices,and may find application in the dynamical excitation control of other nonequilibrium problems with time-periodic driving.

A Brief Introduction to the English Periodical of Contemporary Social Sciences

The English periodical of Contemporary Social Sciences is an English periodical founded by Sichuan Academy of Social Sciences and is published every two months.It was approved by the National Radio and Television Administration of the People’s Republic of China(formerly the State Administration of Press,Publication,Radio,Film and Television of the People’s Republic of China)in March 2016.