A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer

Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.

The Study of Dipivefrin Hydrochloride Ophthalmic Gel

Dipivefrin hydrochloride ophthalmic gel was prepared and the release test and the isolated cornea permeation test of the formulation in vitro were investigated. The release test of the formulation was studied by using permeable membrane. The content and the release amount of Dipivefrin hydrochloride from the gel base were measured by high performance liquid chromatography. The cornea permeation test of the formulation was studied by using isolated rabbit corneas. The formulation release behavior in vitro followed the first-order kinetic equation. The release amount of Dipivefrin hydrochloride raised significantly with less polymer in the formulation. The cornea permeation behavior of the drug in vitro followed the first-order kinetic equation. The eye irritancy of Dipivefrin hydrochloride gel is lower than that of eyedrops.

Reproductive traits of polycystic ovary syndrome in female rhesus monkeys

The objective of this study was to set up a rhesus monkey model of polycystic ovary syndrome（PCOS）,which is globally prevalent among reproductive-aged human women,and to understand the reproductive traits of PCOS female monkeys.Six adult female rhesus monkeys aged 6-10 a,were divided into a PCOS group and a control group.The PCOS group were given two cycles of subcutaneous injections of propionic acid testosterone（PAT）,3.5 mg/kg body weight,on day 1,day 3,and day 5 of the menstrual cycle,respectively,and then given muscle injections of human chorionic gonadotropin（HCG）,350 IU/kg body wtight,on day 7,day 9,and day 11,respectively.Results showed that high levels of serum LH and T [（5.35±0.17） IU/L and（7.58±0.14） ng/mL,respectively],and a high ratio value of LH/FSH（5.35/1.30=4.12） were observed in the PCOS group.No significant differences were found in serum FSH,E2,and P in the PCOS group compared with those of the control.Polycystic ovaries in the PCOS monkeys were recorded by live ultrasound.The blastocysts rates of the PCOS vs.the control were 23.53% vs.66.67%,and there was a significant difference between the two groups.This study shows that PAT coupled with HCG can induce PCOS in rhesus monkeys in the short term.The reproductive features of PCOS monkeys were similar to those of PCOS patients.

Purification and Characterization of Hepatocyte Regeneration Stimulatory Factor from Shark Liver

Aim To purify hepatocyte regeneration stimulatory factor from shark liver and research its molecular feature and activity. Methods and Results Hepatocyte regeneration stimulatory factor (sHRSF) was isolated from healthy shark livers and separated by homogenization, freezing melting, heat treating, centrifugation, and ultrafiltration. HRSF activity was found mainly in the subfraction of molecular weight less than 30 000 daltons. This crude ultrafiltrate was further purified successively by DEAE Sepharose fast flow chromatography, FPLC Resource 30Q, Resource Q and Mono Q chromatography. A single band was displayed on sodium dodecyl sulfate polyacrylamide gel electrophoresis, which corresponds to molecular weight of 14 600 daltons. The characteristic absorption was obtained at the wavelength 276 nm. The isoelectric point was about 5 1. It contained 18 amino acids and the 15 N terminal amino acid residues were LVGPIGAVGPAGKDG. It had a significant activity in stimulating liver to regenerate. Conclusion We obtained an unknown new active protein, that is hepatocyte regeneration stimulatory factor from shark liver (sHRSF).

“刺激性写作”:新世纪文学功用的侧偏

谈及文学的功用,教化、审美和娱乐是文学勿需争辩的三大主要社会功能。消费社会及其商业理念牵引着文学走向泛娱乐化和纵感官时代,以利益刺激为创作诱因、追求满足读者心理和生理刺激性阅读体验的"刺激性写作"应运而生。由此,新世纪文学的功用从主教化与审美日渐趋向重娱乐与消遣的侧偏。本文抛出新世纪文学呈现出的上述问题,对新世纪文学功用纠偏的同时强调消费时代文学创作的深度化。

在思维“碰撞”中激活学生的学习

思维是数学学习的灵魂,而好的情境设计要具有趣味性和思维性。打破学生现有认知结构与外部环境平衡触发学生思维、在求异中激活学生的思维是引导学生意义建构的重要方式。

Stimuli-responsive Membranes： Smart Tools for Controllable Mass-transfer and Separation Processes

As emerging artificial biomimetic membranes, smart or intelligent membranes that are able to respond to environmental stimuli are attracting ever-increasing interests from various fields. Their permeation properties including hydraulic permeability and diffusional permeability can be dramatically controlled or adjusted self-regulatively in response to small chemical and/or physical stimuli in their environments. Such environmental stimuli-responsive smart membranes could find myriad applications in numerous fields ranging from controlled release to separations. Here the trans-membrane mass-transfer and membrane separation is introduced as the beginning to initiate the requirement of smart membranes, and then bio-inspired design of environmental stimuli-responsive smart membranes and four essential elements for smart membranes are introduced and discussed. Next, smart membrane types and their applications as smart tools for controllable mass-transfer in controlled release and separations are reviewed. The research tooics in the near future are also suggested.

EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION ON MOTOR CORTICAL EXCITABILITY AND NEUROFUNCTION AFTER CEREBRAL ISCHEMIA-REPERFUSION INJURY IN RATS

Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n = 10) at different time, while control group (n = 10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed. Results After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly(P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05). Conclusion rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.

DIMENSIONLESS ANALYSIS AND LOCATION OF ELECTRIC FIELD INDUCED BY MAGNETIC COIL

A model of magnetic stimulation is presented for analysis of the spatial distributions of the electric field induced by magnetic coils.Dimensionless analysis is introduced and makes the factors influencing the magnitude of electric field into two parts:c (represents the stimulation conditions),and E 0 (reflects the geometry of coil).By 3 D simulation of the induced electric field of two kinds of coils,the effect of magnetic stimulation can be demonstrated and the factors influencing stimulating focality and depth are identified.The principles for determining the electric field magnitude,focality and magnetic stimulation depth when designing a reasonable coil and stimulator and achieving ideal stimulating effect are discussed.

Kinetics of Coil-to-Globule Transition of DansyI-Labeled Poly（N-isopropyl- acrylamide） Chains in Aqueous Solution

The coil-to-globule transition of thermally sensitive linear poly（N-isopropylacrylamide） （PNIPAM） labeled with dansyl group is induced by 1.54 μm laser pulses （widths10 ns）. The dansyl group is used to follow the transition kinetics because its fluorescence intensity is very sensitive to its micro-environment. As the molar ratio of NIPAM monomer to dansyl group increases from 110 to 300, the effect of covalently attached dansyl fluorophores on the transition decreases. In agreement with our previous study in which we used 8-anilino- l-naphthalensulfonic acid ammonium salt free in water as a fluorescent probe, the current study reveals that the transition has two distinct stages with two characteristic times, namely, Tfast≈0.1 ms, which can be attributed to the nucleation and formation of some ＂pearls＂ （locally contracting segments） on the chain, and tslow≈0.5 ms, which is related to the merging and coarsening of the ＂pearls＂.Tfast is independent of the PNIPAM chain length over a wide range （Mw=2.8× 10^6-4.2 × 10^7 g/mol）. On the other hand, Tslow only slightly increases with the chain length.

Effect of Efferent Vagus Nerve Excitation by Electrical Stimulation on Acute Liver Injury in Rabbits with Endotoxemia

Objective:To study the effect of electrical stimulation of efferent vagus nerve on the acute liver injury induced by endotoxemia in rabbits. Methods:Sixteen rabbits were randomly divided into stimulation group(Group A,n=8) and control group (Group B,n=8).They were subjected to bilateral cervical vagotomy and intravenously challenged by lipopolysaccharide (LPS) (E.coli 0111:B4,DIFCO,USA) at a dose of 100 μg/kg injected within 30 min.The distal end of the left vagus nerve trunk was placed across bipolar electrodes connected to a stimulation module and controlled by an acquisition system.Stimuli with constant voltage (10V,5Hz,5ms) were applied twice to the nerve for 10 min before and after the administration of LPS in Group A.At the time 30,60,120,180,240,300 min before and after infusion of LPS respectively in each animal,blood samples were taken for late measurement of the serum Alanine aminotransferase (ALT),Aspartate aminotransferase (AST),tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10).Immediately after the experiment was finished,autopsy was performed and liver samples were taken to pathologic study. Results:Compared with Group B,the electrical stimulation of efferent vagus nerve could significantly decrease the contents of ALT,AST and TNF-α,but increase the contents of IL-10,in serum of Group A.It could also alleviate inflammation of liver tissue after LPS attack. Conclusion:The results suggest that excitation of the efferent vagus nerve can inhibit the inflammation cascade in liver after LPS challenge.Thus,it might have a protective effect on acute liver damage caused by endotoxemia.

Click-Formed Polymer Gels with Aggregation-Induced Emission and Dual Stimuli-Responsive Behaviors

Stimuli-responsive polymer gels have recently attracted great attention due to their heat/solvent resistance,dimensional stability,and unique sensitivity to external stimuli.In this work,we synthesized thiol-functionalized tetraphenylethylene(TPE)and constructed polymer gels through thiol-ene click reaction.The synthetic process of the polymer gels could be monitored by fluorescence emission of TPE moieties based on aggregation-induced emission mechanism.In addition,due to the dual redox-and acid responsiveness of the polymer gels,in the presence of dithiothreitol and trifluoroacetic acid,fluorescence quenching of the polymer gels can be observed.This stimuli-responsive characteristics endows the polymer gels with potential applications in fluorescent sensing and imaging,cancer diagnosis and selfhealing materials.

pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

Ultrafast Infrared Spectroscopic Study of Microscopic Structural Dynamics in pH Stimulus-Responsive Hydrogels

Hydrogels show versatile properties and are of great interest in the fields of bioelectronics and tissue engineering.Understanding the dynamics of the water molecules trapped in the three-dimensional polymeric networks of the hydrogels is crucial to elucidate their mechanical and swelling properties at the molecular level.In this report,the poly(DMAEMA-co-AA)hydrogels were synthesized and characterized by the macroscopic swelling measurements under different pH conditions.Furthermore,the microscopic structural dynamics of pH stimulus-responsive hydrogels were studied using FTIR and ultrafast IR spectroscopies from the viewpoint of the SCN-anionic solute as the local vibrational reporter.Ultrafast IR spectroscopic measurements showed the time constants of the vibrational population decay of SCN-were increased from 14±1 ps to 20±1 ps when the pH of the hydrogels varied from2.0 to 12.0.Rotational anisotropy measurements further revealed that the rotation of SCNanionic probe was restricted by the three-dimensional network formed in the hydrogels and the rotation of SCN-anionic probe cannot decay to zero especially at the pH of 7.0.These results are expected to provide a molecular-level understanding of the microscopic structure of the cross-linked polymeric network in the pH stimulus-responsive hydrogels.

A new linearly-combined bi-exponential model for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius under electric stimulation in vitro

There was a slow-relaxing tail of skeletal muscles in vitro upon the inhibition of Ca2+-pump by cyclopiazonic acid (CPA). Herein, a new linearly-combined bi-exponential model to resolve this slow-relaxing tail from the fast-relaxing phase was investigated for kinetic analysis of the isometric relaxation process of Bufo gastrocnemius in vitro, in comparison to the single exponential model and the classical bi-exponential model. During repetitive stimulations at a 2-s interval by square pulses of a 2-ms duration at 12 V direct currency (DC), the isometric tension of Bufo gastrocnemius was recorded at 100 Hz. The relaxation curve with tensions falling from 90% of the peak to the 15th datum before next stimulation was analyzed by three exponential models using a program in MATLAB 6.5. Both the goodness of fit and the distribution of the residuals for the best fitting sup- ported the comparable validity of this new bi-exponential model for kinetic analysis of the relaxation process of the control muscles. After CPA treatment, however, this new bi-exponential model showed an obvious statistical superiority for kinetic analysis of the muscle relaxation process, and it gave the estimated rest tension consistent to that by experimentation, whereas both the classical bi-exponential model and the single exponential model gave biased rest tensions. Moreover, after the treatment of muscles by CPA, both the single exponential model and the classical bi-exponential model yielded lowered relaxation rates, nevertheless, this new bi-exponential model had relaxation rates of negligible changes except much higher rest tensions. These results suggest that this novel linearly-combined bi-exponential model is desirable for kinetic analysis of the relaxation process of muscles with altered Ca2+-pumping activity.

The Effects of Lei Gong Teng on Reproductive Hormones

The serum reproductive hormone levels were examined with radioimmunoassay in women of child-bearing age before and after treatment with the prescriptions containing Lei Gong Teng ([symbol: see text] Radix Tripterygii Wilfordii). The results showed that Lei Gong Teng could induce amenorrhea, but it was reversible.

Effects of quercetin on hepatocyte stimulating factor production by mouse peritoneal macrophages

Objective: To study the effects of quercetin on hepatocyte stimulating factor production from mouse peritoneal macrophages. Methods: Hepatocyte stimulating factor was evaluated by the amount of fibrinogen synthesized in Hep3B cells. Interleukin-6 activity was measured by B9 cell proliferation methyl thiazolyl tetrazolium colorimetric method. Hep3B cell supernatant fibrinogen was quantitated with ELISA. Results: LPS induced the synthesis of hepatocyte stimulating factor in mouse peritoneal macrophages, and hepatocyte stimulating factor promotes the synthesis of fibrinogen from Hep3B cells. Quercetin(5 to 40μmol/ L) inhibited the synthesis of hepatocyte stimulating factor stimulated by LPS. Quercetin(5 to 20μmol/ L) inhibited release of interleukin-6 from mouse peritoneal macrophages induced by 0. 5 g/ L fibrin fibrinogen degradation products. Conclusion: Quercetin inhibits the synthesis of hepatocyte stimulating factor in macrophages.

Suppression of angiotensin Ⅱ stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (ECAR), which was measured by Cytosensor microphysiometry, was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals. The ability of AT-Ⅱ to promote formation of inositol phosphates, the second messenger produced by the activation of Gq-coupled receptors, was also considerably suppressed in the cirrhotic VSMCs. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-Ⅱ was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs. Taken together, our data clearly demonstrated that the functional responses to AT-Ⅱ was severely suppressed in aortic VSMCs in cirrhosis, indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

Study Under AC Stimulation on Excitement Properties of Weighted Small-World Biological Neural Networks with Side-Restrain Mechanism

In this paper, we propose a new model of weighted small-world biological neural networks based on biophysical Hodgkin-Huxley neurons with side-restrain mechanism. Then we study excitement properties of the model under alternating current （AC） stimulation. The study shows that the excitement properties in the networks are preferably consistent with the behavior properties of a brain nervous system under different AC stimuli, such as refractory period and the brain neural excitement response induced by different intensities of noise and coupling. The results of the study have reference worthiness for the brain nerve electrophysiology and epistemological science.

Light and temperature dual responsive pesticide release system based on mesoporous silica nanoparticles modified by dopamine

A light and temperature dual responsive copolymer,poly(7-(4-vinylbenzy-loxyl)-4-methylcoumarin-co-N vinyl caprolactam-co-tri(ethylene glycol)methyl ether methacrylate)(PVNM),was grafted on the surface of dopamine based mesoporous silica nanoparticles(MSNs).The resulting polymer brush,MSNs-g-PVNM,was characterized by FT-IR,TEM,TGA and XPS.The dual responsive behaviors of MSNs-g-PVNM were systematically studied.With imidacloprid as the model guest pesticide,the loading percentage and loading efficiency of the polymer brush were determined as 9.2%and 40.6%,respectively.The release efficiency of imidacloprid in MSNs-g-PVNM was the lowest value of 5.4%at 20℃ and 365 nm,and it reached the highest value of 52.4%at 50℃ and 254 nm.The loss percentage of imidacloprid on the leaves contained imidacloprid-loaded MSNs-g-PVNM(8.4%)was much less than that contained only imidacloprid(25.2%)after three rinses.It was confirmed that the release process of imidacloprid was well regulated through changing external conditions such as light and temperature.