The flow around a square cylinder with a synthetic jet positioned at the rear surface is numerically investigated with the unsteady Reynolds-averaged Navier-Stokes(URANS)method.Instead of the typical sinusoidal wave,a...The flow around a square cylinder with a synthetic jet positioned at the rear surface is numerically investigated with the unsteady Reynolds-averaged Navier-Stokes(URANS)method.Instead of the typical sinusoidal wave,a bi-frequency signal is adopted to generate the synthetic jet.The bi-frequency signal consists of a basic sinusoidal wave and a high-frequency wave.Cases with various amplitudes of the high-frequency component are simulated.It is found that synthetic jets actuated by bi-frequency signals can realize better drag reduction with lower energy consumption when appropriate parameter sets are applied.A new quantity,i.e.,the actuation efficiency Ae,is used to evaluate the controlling efficiency.The actuation efficiency Ae reaches its maximum of 0.2668 when the amplitude of the superposed high-frequency signal is 7.5%of the basic signal.The vortex structures and frequency characteristics are subsequently analyzed to investigate the mechanism of the optimization of the bi-frequency signal.When the synthetic jet is actuated by a single-frequency signal with a characteristic velocity of 0.112 m/s,the wake is asymmetrical.The alternative deflection of vortex pairs and the peak at half of the excitation frequency in the power spectral density(PSD)function are detected.In the bi-frequency cases with the same characteristic velocity,the wake gradually turns to be symmetrical with the increase in the amplitude of the high-frequency component.Meanwhile,the deflection of the vortex pairs and the peak at half of the excitation frequency gradually disappear as well.展开更多
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
To explore the feasibility and superiority of iodine delivery rate(IDR)and tube voltage determined by patients'body mass index(BMI)in coronary CT angiography(CCTA),a total of 1567 patients undertaking CCTA during ...To explore the feasibility and superiority of iodine delivery rate(IDR)and tube voltage determined by patients'body mass index(BMI)in coronary CT angiography(CCTA),a total of 1567 patients undertaking CCTA during Feb.and Dec.2016 were enrolled and divided into two groups.In the control group,the IDR and tube voltage were fixed,while in the experimental group,the IDR and tube voltage were determined by patients,BMI.The volume of iodinated contrast media(ICM),extravasation rate,extravasation volume,extravasation recovery interval,incidence rate of adverse reactions,effective dose(ED)and image quality of the two groups were compared.The experiments demonstrated that the ICM volume,extravasation rate,extravasation volume,extravasation recovery interval,incidence of adverse reactions and ED were lower or shorter in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,there were no significant differences in the mean CT value,image noise,signal to noise ratio and contrast to noise ratio between the two groups(all P<0.05),which were consistent with the diagnosticians*subjective evaluation outcomes.Our findings suggested that in CCTA,it is feasible to determine the IDR and tube voltage based on patients'BMI;low tube voltage and IDR are superior to the fixed tube voltage and IDR and are worthy of clinical promotion.展开更多
Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been show...Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor α and interleukin-1β in the supernatant. Furthermore, Atsttrin significantly reduced the levels of phospho-nuclear factor kappa B inhibitor α in the brain of lipopolysaccharide-treated progranulin knockout mice and astrocytes, and it decreased the expression of nuclear factor kappa B2 in astrocytes. Collectively, our findings show that the anti-neuroinflammatory effect of Atsttrin involves inhibiton of the nuclear factor kappa B signaling pathway, and they suggest that Atsttrin may have clinical potential in neuroinflammatory therapy.展开更多
BACKGROUND The molecular mechanisms underlying anorectal malformations(ARM)are not fully established.Circular RNAs(circRNAs)are new born non-coding RNAs,and their role in ARM is unclear.We assumed that rno_circ_000513...BACKGROUND The molecular mechanisms underlying anorectal malformations(ARM)are not fully established.Circular RNAs(circRNAs)are new born non-coding RNAs,and their role in ARM is unclear.We assumed that rno_circ_0005139 influences apoptosis and proliferation by acting as a miR-324-3p sponge,and downregulating Wnt5a in ARM.AIM To identify the differential expression of circRNAs and mRNAs in a rat ARM model.METHODS Sixty-six pregnant Wistar rats were randomly divided into two groups:ARM group(2-imidazolidinethione-induced)and control groups.Embryos were harvested by cesarean delivery,and anorectal tissue was taken on embryonic days 16(E16),17(E17),19(E19),and 21(E21).RNA sequencing and gene microarray analysis was used to identify differentially expressed circRNAs and mRNAs in the ARM in a rat model.We selected 6 circRNAs and 3 mRNAs in the Wnt signal pathway from the result of the RNA sequencing and gene microarray analysis,and quantitative reverse transcription polymerase chain reaction was performed to evaluate their tissue expression.According to bioinformatics prediction,rno_circ_0005139 acted as a miR-324-3p sponge to regulate the expression of Wnt5a.We chose rno_circ_0005139 and Wnt5a as the final candidates.We tested the function of rno_circ_0005139 and the binding sites between rno_circ_0005139 and miR-324-3p,miR-324-3p and Wnt5a by luciferase assays.Co-transfection of rno_circ_0005139 and miR-324-3p was to verify their functional consistency.RESULTS We identified 38 upregulated and 42 downregulated circRNAs on E17(P<0.05),and 301 mRNAs were upregulated and 256 downregulated in the ARM on E17(P<0.05,fold-change>2.0).We found that rno_circ_0006880 and rno_circ_0011386 were upregulated,whereas rno_circ_0000436,rno_circ_0005139,rno_circ_0009285,rno_circ_0014367,Wnt5a,Wnt10b,and Wnt2b were downregulated in ARM tissues.According to bioinformatics prediction,rno_circ_0005139 acted as a miR-324-3p sponge to regulate the expression of Wnt5a.We chose rno_circ_0005139 and Wnt5a as the final candidates.Because the role and molecular mechanism of rno_circ_0005139 are poorly understood,its effect on apoptosis and proliferation was investigated by in vitro plasmid transfection.A luciferase experiment showed that rno_circ_0005139 could bind with miR-324-3p,which negatively regulated Wnt5a expression.The expression of miR-324-3p was significantly higher in ARM anorectal tissues than that in control group on E17 and E19;Wnt5a expression showed the opposite trend.In addition,a miR-324-3p inhibitor attenuated the effects of rno_circ_0005139 knockdown on ARM development.CONCLUSION Rno_circ_0005139 influences cell proliferation and apoptosis by acting as a miR-324-3p sponge,thereby downregulating Wnt5a in ARM.Accordingly,rno_circ_0005139,miR-324-3p,and Wnt5a could be targeted therapeutic factors for ARM.展开更多
Peri-implantitis is one of the most important biological complications in the field of oral implantology.Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prev...Peri-implantitis is one of the most important biological complications in the field of oral implantology.Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prevention and treatment.The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated.Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue.Notably,the concentration of titanium particles increases significantly at peri-implantitis sites,suggesting titanium particles as a potential risk factor for the condition.Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement.However,it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues.This review summarizes the distribution of titanium particles around the implant,the potential roles in peri-implantitis and the prevalent prevention strategies,which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.展开更多
Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined t...Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.展开更多
Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 83...Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions.The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution,respectively.The optimal cut-offvalue of SII was determined,and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort.The propensity score matching(PSM)method was applied to minimize the confounding effects of unbalanced covariables.Results:The optimal cut-offvalue of the SII in the training cohort was 686,which was confirmed using the vali-dation cohort.Multivariate analysis showed that both before and after PSM,SII values>686 were independently associated with worse progression-free survival(PFS)ratio in both cohorts(before PSM,P=0.008 and P=0.008;after PSM,P=0.008 and P=0.007,respectively).Based on the analysis of independent prognostic factors of SII and N stage,we developed a categorical risk stratification model,which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival(DMFS)in the training cohort.There was no significant difference in PFS between RT alone and combined therapies within the low-and intermediate-risk groups(5-year PFS,77.5%vs.75.3%,P=0.275).Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies(5-year PFS,64.9%vs.40.3%,P=0.003).Conclusion:Pretreatment SII predicts PFS of patients with non-metastatic NPC.Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.展开更多
The exact physical modeling for scattered light modulation is critical in phototherapy,biomedical imaging,and free-space optical communications.In particular,the angular spectrum modeling of scattered light has attrac...The exact physical modeling for scattered light modulation is critical in phototherapy,biomedical imaging,and free-space optical communications.In particular,the angular spectrum modeling of scattered light has attracted considerable attention,but the existing angular spectrum models neglect the polarization of photons,degrading their performance.Here,we propose a full-polarization angular spectrum model(fpASM)to take the polarization into account.This model involves a combination of the optical field changes and free-space angular spectrum diffraction,and enables an investigation of the influence of polarization-related factors on the performance of scattered light modulation.By establishing the relationship between various model parameters and macroscopic scattering properties,our model can effectively characterize various depolarization conditions.As a demonstration,we apply the model in the time-reversal data transmission and anti-scattering light focusing.Our method allows the analysis of various depolarization scattering events and benefits applications related to scattered light modulation.展开更多
Accurately measuring the complex transmission matrix(CTM) of the scattering medium(SM) holds critical significance for applications in anti-scattering optical imaging, phototherapy, and optical neural networks. Nonint...Accurately measuring the complex transmission matrix(CTM) of the scattering medium(SM) holds critical significance for applications in anti-scattering optical imaging, phototherapy, and optical neural networks. Noninterferometric approaches, utilizing phase retrieval algorithms, can robustly extract the CTM from the speckle patterns formed by multiple probing fields traversing the SM. However, in cases where an amplitude-type spatial light modulator is employed for probing field modulation, the absence of phase control frequently results in the convergence towards a local optimum, undermining the measurement accuracy. Here, we propose a high-accuracy CTM retrieval(CTMR) approach based on regional phase differentiation(RPD). It incorporates a sequence of additional phase masks into the probing fields, imposing a priori constraints on the phase retrieval algorithms. By distinguishing the variance of speckle patterns produced by different phase masks, the RPD-CTMR can effectively direct the algorithm towards a solution that closely approximates the CTM of the SM. We built a prototype of a digital micromirror device modulated RPD-CTMR. By accurately measuring the CTM of diffusers, we achieved an enhancement in the peak-to-background ratio of anti-scattering focusing by a factor of 3.6, alongside a reduction in the bit error rate of anti-scattering image transmission by a factor of 24. Our proposed approach aims to facilitate precise modulation of scattered optical fields, thereby fostering advancements in diverse fields including high-resolution microscopy, biomedical optical imaging, and optical communications.展开更多
Optical reservoir computing(ORC)offers advantages,such as high computational speed,low power consumption,and high training speed,so it has become a competitive candidate for time series analysis in recent years.The cu...Optical reservoir computing(ORC)offers advantages,such as high computational speed,low power consumption,and high training speed,so it has become a competitive candidate for time series analysis in recent years.The current ORC employs single-dimensional encoding for computation,which limits input resolution and introduces extraneous information due to interactions between optical dimensions during propagation,thus constraining performance.Here,we propose complex-value encoding-based optoelectronic reservoir computing(CE-ORC),in which the amplitude and phase of the input optical field are both modulated to improve the input resolution and prevent the influence of extraneous information on computation.In addition,scale factors in the amplitude encoding can fine-tune the optical reservoir dynamics for better performance.We built a CE-ORC processing unit with an iteration rate of up to∼1.2 kHz using high-speed communication interfaces and field programmable gate arrays(FPGAs)and demonstrated the excellent performance of CE-ORC in two time series prediction tasks.In comparison with the conventional ORC for the Mackey–Glass task,CE-ORC showed a decrease in normalized mean square error by∼75%.Furthermore,we applied this method in a weather time series analysis and effectively predicted the temperature and humidity within a range of 24 h.展开更多
Background： Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema mod...Background： Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model. Methods： A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography （FP）, optical coherence tomography （OCT）, and fluoresce in fundus angiography （FFA） at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay （ELISA） and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1. Results： Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group （26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P 〈 0.01）; the mean RT （278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P 〈 0.05） and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 （P 〈 0.05）. Conclusions： This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.展开更多
Speed and enhancement are the two most important metrics for anti-scattering light focusing by wavefront shaping(WS),which requires a spatial light modulator with a large number of modulation modes and a fast speed of...Speed and enhancement are the two most important metrics for anti-scattering light focusing by wavefront shaping(WS),which requires a spatial light modulator with a large number of modulation modes and a fast speed of response.Among the commercial modulators,the digital-micromirror device(DMD)is the sole solution providing millions of modulation modes and a pattern rate higher than 20 kHz.Thus,it has the potential to accelerate the process of anti-scattering light focusing with a high enhancement.Nevertheless,modulating light in a binary mode by the DMD restricts both the speed and enhancement seriously.Here,we propose a multi-pixel encoded DMD-based WS method by combining multiple micromirrors into a single modulation unit to overcome the drawbacks of binary modulation.In addition,to efficiently optimize the wavefront,we adopted separable natural evolution strategies(SNES),which could carry out a global search against a noisy environment.Compared with the state-of-the-art DMD-based WS method,the proposed method increased the speed of optimization and enhancement of focus by a factor of 179 and 16,respectively.In our demonstration,we achieved 10 foci with homogeneous brightness at a high speed and formed W-and S-shape patterns against the scattering medium.The experimental results suggest that the proposed method will pave a new avenue for WS in the applications of biomedical imaging,photon therapy,optogenetics,dynamic holographic display,etc.展开更多
基金supported by the National Natural Science Foundation of China(No.11721202)。
文摘The flow around a square cylinder with a synthetic jet positioned at the rear surface is numerically investigated with the unsteady Reynolds-averaged Navier-Stokes(URANS)method.Instead of the typical sinusoidal wave,a bi-frequency signal is adopted to generate the synthetic jet.The bi-frequency signal consists of a basic sinusoidal wave and a high-frequency wave.Cases with various amplitudes of the high-frequency component are simulated.It is found that synthetic jets actuated by bi-frequency signals can realize better drag reduction with lower energy consumption when appropriate parameter sets are applied.A new quantity,i.e.,the actuation efficiency Ae,is used to evaluate the controlling efficiency.The actuation efficiency Ae reaches its maximum of 0.2668 when the amplitude of the superposed high-frequency signal is 7.5%of the basic signal.The vortex structures and frequency characteristics are subsequently analyzed to investigate the mechanism of the optimization of the bi-frequency signal.When the synthetic jet is actuated by a single-frequency signal with a characteristic velocity of 0.112 m/s,the wake is asymmetrical.The alternative deflection of vortex pairs and the peak at half of the excitation frequency in the power spectral density(PSD)function are detected.In the bi-frequency cases with the same characteristic velocity,the wake gradually turns to be symmetrical with the increase in the amplitude of the high-frequency component.Meanwhile,the deflection of the vortex pairs and the peak at half of the excitation frequency gradually disappear as well.
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
文摘To explore the feasibility and superiority of iodine delivery rate(IDR)and tube voltage determined by patients'body mass index(BMI)in coronary CT angiography(CCTA),a total of 1567 patients undertaking CCTA during Feb.and Dec.2016 were enrolled and divided into two groups.In the control group,the IDR and tube voltage were fixed,while in the experimental group,the IDR and tube voltage were determined by patients,BMI.The volume of iodinated contrast media(ICM),extravasation rate,extravasation volume,extravasation recovery interval,incidence rate of adverse reactions,effective dose(ED)and image quality of the two groups were compared.The experiments demonstrated that the ICM volume,extravasation rate,extravasation volume,extravasation recovery interval,incidence of adverse reactions and ED were lower or shorter in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,there were no significant differences in the mean CT value,image noise,signal to noise ratio and contrast to noise ratio between the two groups(all P<0.05),which were consistent with the diagnosticians*subjective evaluation outcomes.Our findings suggested that in CCTA,it is feasible to determine the IDR and tube voltage based on patients'BMI;low tube voltage and IDR are superior to the fixed tube voltage and IDR and are worthy of clinical promotion.
基金supported by the National Natural Science Foundation of China,No.81572191(to LC)and 81601067(to HZ)
文摘Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor α and interleukin-1β in the supernatant. Furthermore, Atsttrin significantly reduced the levels of phospho-nuclear factor kappa B inhibitor α in the brain of lipopolysaccharide-treated progranulin knockout mice and astrocytes, and it decreased the expression of nuclear factor kappa B2 in astrocytes. Collectively, our findings show that the anti-neuroinflammatory effect of Atsttrin involves inhibiton of the nuclear factor kappa B signaling pathway, and they suggest that Atsttrin may have clinical potential in neuroinflammatory therapy.
基金Supported by the National Natural Science Foundation of China,No.81671503.Institutional animal care and use committee statement:All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals(licence No.2016PS045K)We would like to thank Luo K, biostatistician at the MOE-Shanghai Key Laboratory ofChildren‘s Environmental Health in Shanghai Jiao Tong University School ofMedicine, for reviewing the content of our manuscript to confirm appropriateness ofbiostatistical methods for study design.
文摘BACKGROUND The molecular mechanisms underlying anorectal malformations(ARM)are not fully established.Circular RNAs(circRNAs)are new born non-coding RNAs,and their role in ARM is unclear.We assumed that rno_circ_0005139 influences apoptosis and proliferation by acting as a miR-324-3p sponge,and downregulating Wnt5a in ARM.AIM To identify the differential expression of circRNAs and mRNAs in a rat ARM model.METHODS Sixty-six pregnant Wistar rats were randomly divided into two groups:ARM group(2-imidazolidinethione-induced)and control groups.Embryos were harvested by cesarean delivery,and anorectal tissue was taken on embryonic days 16(E16),17(E17),19(E19),and 21(E21).RNA sequencing and gene microarray analysis was used to identify differentially expressed circRNAs and mRNAs in the ARM in a rat model.We selected 6 circRNAs and 3 mRNAs in the Wnt signal pathway from the result of the RNA sequencing and gene microarray analysis,and quantitative reverse transcription polymerase chain reaction was performed to evaluate their tissue expression.According to bioinformatics prediction,rno_circ_0005139 acted as a miR-324-3p sponge to regulate the expression of Wnt5a.We chose rno_circ_0005139 and Wnt5a as the final candidates.We tested the function of rno_circ_0005139 and the binding sites between rno_circ_0005139 and miR-324-3p,miR-324-3p and Wnt5a by luciferase assays.Co-transfection of rno_circ_0005139 and miR-324-3p was to verify their functional consistency.RESULTS We identified 38 upregulated and 42 downregulated circRNAs on E17(P<0.05),and 301 mRNAs were upregulated and 256 downregulated in the ARM on E17(P<0.05,fold-change>2.0).We found that rno_circ_0006880 and rno_circ_0011386 were upregulated,whereas rno_circ_0000436,rno_circ_0005139,rno_circ_0009285,rno_circ_0014367,Wnt5a,Wnt10b,and Wnt2b were downregulated in ARM tissues.According to bioinformatics prediction,rno_circ_0005139 acted as a miR-324-3p sponge to regulate the expression of Wnt5a.We chose rno_circ_0005139 and Wnt5a as the final candidates.Because the role and molecular mechanism of rno_circ_0005139 are poorly understood,its effect on apoptosis and proliferation was investigated by in vitro plasmid transfection.A luciferase experiment showed that rno_circ_0005139 could bind with miR-324-3p,which negatively regulated Wnt5a expression.The expression of miR-324-3p was significantly higher in ARM anorectal tissues than that in control group on E17 and E19;Wnt5a expression showed the opposite trend.In addition,a miR-324-3p inhibitor attenuated the effects of rno_circ_0005139 knockdown on ARM development.CONCLUSION Rno_circ_0005139 influences cell proliferation and apoptosis by acting as a miR-324-3p sponge,thereby downregulating Wnt5a in ARM.Accordingly,rno_circ_0005139,miR-324-3p,and Wnt5a could be targeted therapeutic factors for ARM.
基金the National Natural Science Foundation of China(No.82170992,No.82201051 and No.82370990)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(WKJ-ZJ-2335)+1 种基金Innovative Talent of Zhejiang Provincial Health Commission,China Postdoctoral Science Foundation(2022M722742)2022 General Scientific Research Project of Zhejiang Education Department(Natural Science)(Y202249943).
文摘Peri-implantitis is one of the most important biological complications in the field of oral implantology.Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prevention and treatment.The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated.Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue.Notably,the concentration of titanium particles increases significantly at peri-implantitis sites,suggesting titanium particles as a potential risk factor for the condition.Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement.However,it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues.This review summarizes the distribution of titanium particles around the implant,the potential roles in peri-implantitis and the prevalent prevention strategies,which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.
文摘Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.
文摘Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions.The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution,respectively.The optimal cut-offvalue of SII was determined,and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort.The propensity score matching(PSM)method was applied to minimize the confounding effects of unbalanced covariables.Results:The optimal cut-offvalue of the SII in the training cohort was 686,which was confirmed using the vali-dation cohort.Multivariate analysis showed that both before and after PSM,SII values>686 were independently associated with worse progression-free survival(PFS)ratio in both cohorts(before PSM,P=0.008 and P=0.008;after PSM,P=0.008 and P=0.007,respectively).Based on the analysis of independent prognostic factors of SII and N stage,we developed a categorical risk stratification model,which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival(DMFS)in the training cohort.There was no significant difference in PFS between RT alone and combined therapies within the low-and intermediate-risk groups(5-year PFS,77.5%vs.75.3%,P=0.275).Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies(5-year PFS,64.9%vs.40.3%,P=0.003).Conclusion:Pretreatment SII predicts PFS of patients with non-metastatic NPC.Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.
基金National Natural Science Foundation of China(62205189,62375171)Fundamental Research Funds for the Central Universities+3 种基金Shanghai Pujiang Program(22PJ1407500)Shanghai Jiao Tong University 2030Initiative(WH510363001-10)Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(SL2022ZD205)Science Foundation of Donghai Laboratory(DH-2022KF01001)。
文摘The exact physical modeling for scattered light modulation is critical in phototherapy,biomedical imaging,and free-space optical communications.In particular,the angular spectrum modeling of scattered light has attracted considerable attention,but the existing angular spectrum models neglect the polarization of photons,degrading their performance.Here,we propose a full-polarization angular spectrum model(fpASM)to take the polarization into account.This model involves a combination of the optical field changes and free-space angular spectrum diffraction,and enables an investigation of the influence of polarization-related factors on the performance of scattered light modulation.By establishing the relationship between various model parameters and macroscopic scattering properties,our model can effectively characterize various depolarization conditions.As a demonstration,we apply the model in the time-reversal data transmission and anti-scattering light focusing.Our method allows the analysis of various depolarization scattering events and benefits applications related to scattered light modulation.
基金National Natural Science Foundation of China(62305208,62375171)Shanghai Pujiang Program(22PJ1407500)+2 种基金Shanghai Jiao Tong University 2030 Initiative(WH510363001-10)Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(SL2022ZD205)Science Foundation of Donghai Laboratory(DH-2022KF01001)。
文摘Accurately measuring the complex transmission matrix(CTM) of the scattering medium(SM) holds critical significance for applications in anti-scattering optical imaging, phototherapy, and optical neural networks. Noninterferometric approaches, utilizing phase retrieval algorithms, can robustly extract the CTM from the speckle patterns formed by multiple probing fields traversing the SM. However, in cases where an amplitude-type spatial light modulator is employed for probing field modulation, the absence of phase control frequently results in the convergence towards a local optimum, undermining the measurement accuracy. Here, we propose a high-accuracy CTM retrieval(CTMR) approach based on regional phase differentiation(RPD). It incorporates a sequence of additional phase masks into the probing fields, imposing a priori constraints on the phase retrieval algorithms. By distinguishing the variance of speckle patterns produced by different phase masks, the RPD-CTMR can effectively direct the algorithm towards a solution that closely approximates the CTM of the SM. We built a prototype of a digital micromirror device modulated RPD-CTMR. By accurately measuring the CTM of diffusers, we achieved an enhancement in the peak-to-background ratio of anti-scattering focusing by a factor of 3.6, alongside a reduction in the bit error rate of anti-scattering image transmission by a factor of 24. Our proposed approach aims to facilitate precise modulation of scattered optical fields, thereby fostering advancements in diverse fields including high-resolution microscopy, biomedical optical imaging, and optical communications.
基金the National Natural Science Foundation of China(Grant Nos.62375171,62305208,62205189,62105203,and 62405182)the Shanghai Pujiang Program(Grant No.22PJ1407500)+4 种基金the Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(SJTU)(Grant No.SL2022ZD205)the National Key Research and Development Program of China(Grant No.2022YFC2806600)the Science Foundation of Donghai Laboratory(Grant Nos.DH-2022KF01001 and DH-2022KF01005)the Startup Fund for Young Faculty at SJTU(Grant No.24X010500120)the Science and Technology Commission of Shanghai Municipality(Grant No.20DZ2220400).
文摘Optical reservoir computing(ORC)offers advantages,such as high computational speed,low power consumption,and high training speed,so it has become a competitive candidate for time series analysis in recent years.The current ORC employs single-dimensional encoding for computation,which limits input resolution and introduces extraneous information due to interactions between optical dimensions during propagation,thus constraining performance.Here,we propose complex-value encoding-based optoelectronic reservoir computing(CE-ORC),in which the amplitude and phase of the input optical field are both modulated to improve the input resolution and prevent the influence of extraneous information on computation.In addition,scale factors in the amplitude encoding can fine-tune the optical reservoir dynamics for better performance.We built a CE-ORC processing unit with an iteration rate of up to∼1.2 kHz using high-speed communication interfaces and field programmable gate arrays(FPGAs)and demonstrated the excellent performance of CE-ORC in two time series prediction tasks.In comparison with the conventional ORC for the Mackey–Glass task,CE-ORC showed a decrease in normalized mean square error by∼75%.Furthermore,we applied this method in a weather time series analysis and effectively predicted the temperature and humidity within a range of 24 h.
文摘Background： Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model. Methods： A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography （FP）, optical coherence tomography （OCT）, and fluoresce in fundus angiography （FFA） at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay （ELISA） and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1. Results： Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group （26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P 〈 0.01）; the mean RT （278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P 〈 0.05） and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 （P 〈 0.05）. Conclusions： This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.
基金Shanghai Municipal of Science and Technology Project(No.20JC1419500)Foundation of National Facility for Translational Medicine(Shanghai)(No.TMSK-2020-129)+2 种基金Shanghai Pujiang Program(NO.20PJ 1408700)National Natural Science Foundation of China(No.62005007)the Fundamental Research Funds for the Central Universities(Beihang University).
文摘Speed and enhancement are the two most important metrics for anti-scattering light focusing by wavefront shaping(WS),which requires a spatial light modulator with a large number of modulation modes and a fast speed of response.Among the commercial modulators,the digital-micromirror device(DMD)is the sole solution providing millions of modulation modes and a pattern rate higher than 20 kHz.Thus,it has the potential to accelerate the process of anti-scattering light focusing with a high enhancement.Nevertheless,modulating light in a binary mode by the DMD restricts both the speed and enhancement seriously.Here,we propose a multi-pixel encoded DMD-based WS method by combining multiple micromirrors into a single modulation unit to overcome the drawbacks of binary modulation.In addition,to efficiently optimize the wavefront,we adopted separable natural evolution strategies(SNES),which could carry out a global search against a noisy environment.Compared with the state-of-the-art DMD-based WS method,the proposed method increased the speed of optimization and enhancement of focus by a factor of 179 and 16,respectively.In our demonstration,we achieved 10 foci with homogeneous brightness at a high speed and formed W-and S-shape patterns against the scattering medium.The experimental results suggest that the proposed method will pave a new avenue for WS in the applications of biomedical imaging,photon therapy,optogenetics,dynamic holographic display,etc.
