Mechanism of acupoint penetration acupuncture therapy regulating chondrocyte autophagy via the PI3K/Akt-mTOR pathway in KOA rats

Objective:To investigate whether acupoint penetration acupuncture(APA)could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis(KOA)rats.Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution.Forty male Sprague-Dawley rats were randomly assigned to blank control,model,APA,electro-acupuncture(EA),and sham model groups(n=8)and those in the APA and EA groups received their respective therapies.Following completion of the treatment course,histological examinations of cartilage and muscle were conducted.Levels of apoptosis-and autophagy-related factors,including Bax,Bcl-2,mTOR,ULK-1,and Beclin-1 protein,and mRNAs were assessed.Additionally,β-endorphin(β-EP)concentrations in the brain and serum were measured.Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group.APA inhibited cartilage degeneration by modulating the expression of apoptosis-and autophagy-related proteins and mRNA,thus preventing chondrocyte apoptosis.In the APA group,Bax and mTOR protein levels were significantly lower than those in the model group(both P=.024).Conversely,the Bcl-2 expression level was significantly higher than that in the EA group(P=.035).Additionally,ULK-1 expression was significantly lower than that in the EA group(P=.045).The mRNA level of Bax was significantly higher than that in the blank control group(P<.001).However,Beclin-1 levels were significantly higher than those in both the model and EA groups(both P<.001).ELISA results showed a significant decrease in the concentration ofβ-EP in the brains of the rats in the APA group compared with those in the model group(P=.032).Conclusions: APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.

Hybrid reconstruction framework for model-based multispectral bioluminescence tomography based on Alpha-divergence

Bioluminescence tomography(BLT)is a promising imaging modality that can provide noninvasive three-dimensional visualization information on tumor distribution.In BLT reconstruction,the widely used methods based on regularization or greedy strategy face problems such as over-sparsity,over-smoothing,spatial discontinuity,poor robustness,and poor multi-target resolution.To deal with these problems,combining the advantages of the greedy strategies as well as regularization methods,we propose a hybrid reconstruction framework for model-based multispectral BLT using the support set of a greedy strategy as a feasible region and the Alpha-divergence to combine the weighted solutions obtained by L1-norm and L2-norm regularization methods.In numerical simulations with digital mouse and in vivo experiments,the results show that the proposed framework has better localization accuracy,spatial resolution,and multi-target resolution.

Adaptive hp finite element method for fluorescence molecular tomography with simplified spherical harmonics approximation

Recently,the simplified spherical harmonics equations(SP)model has at tracted much att entionin modeling the light propagation in small tissue ggeometriesat visible and near-infrared wave-leng ths.In this paper,we report an eficient numerical method for fluorescence moleeular tom-ography(FMT)that combines the advantage of SP model and adaptive hp finite elementmethod(hp-FEM).For purposes of comparison,hp-FEM and h-FEM are,respectively applied tothe reconstruction pro cess with diffusion approximation and SPs model.Simulation experiments on a 3D digital mouse atlas and physical experiments on a phantom are designed to evaluate thereconstruction methods in terms of the location and the reconstructed fluorescent yield.Theexperimental results demonstrate that hp-FEM with SPy model,yield more accurate results thanh-FEM with difusion approximation model does.The phantom experiments show the potentialand feasibility of the proposed approach in FMT applications.

Sparse reconstruction for fluorescence molecular tomography via a fast iterative algorithm

Fluorescence molecular tomography(FMT)is a fast-developing optical imaging modalitythat has great potential in early diagnosis of disease and drugs development.However,recon-struction algorithms have to address a highly ill-posed problem to fulfll 3D reconstruction inFMT.In this contribution,we propose an efficient iterative algorithm to solve the large-scalereconstruction problem,in which the sparsity of fluorescent targets is taken as useful a prioriinformation in designing the reconstruction algorithm.In the implementation,a fast sparseapproximation scheme combined with a stage-wise learning strategy enable the algorithm to dealwith the ill-posed inverse problem at reduced computational costs.We validate the proposed fastiterative method with numerical simulation on a digital mouse model.Experimental results demonstrate that our method is robust for different finite element meshes and different Poissonnoise levels.

Use of DNA metabarcoding of bird pellets in understanding raptor diet on the Qinghai-Tibetan Plateau of China

Background:Diet analysis is essential to understanding the functional role of large bird species in food webs.Mor-phological analysis of regurgitated bird pellet contents is time intensive and may underestimate biodiversity.DNA metabarcoding has the ability to circumvent these issues,but has yet to be done.Methods:We present a pilot study using DNA metabarcoding of MT-RNR1 and MT-CO1 markers to determine the species of origin and prey of 45 pellets collected in Qinghai and Gansu Provinces,China.Results:We detected four raptor species[Eurasian Eagle Owl(Bubo bubo),Saker Falcon(Falco cherrug),Steppe Eagle(Aquila nipalensis),and Upland Buzzard(Buteo hemilasius)]and 11 unique prey species across 10 families and 4 classes.Mammals were the greatest detected prey class with Plateau Pika(Ochotona curzoniae)being the most frequent.Observed Shannon’s and Simpson’s diversity for Upland Buzzard were 1.089 and 0.479,respectively,while expected values were 1.312±0.266 and 0.485±0.086.For Eurasian Eagle Owl,observed values were 1.202 and 0.565,while expected values were 1.502±0.340 and 0.580±0.114.Interspecific dietary niche partitioning between the two spe-cies was not detected.Conclusions:Our results demonstrate successful use of DNA metabarcoding for understanding diet via a novel noninvasive sample type to identify common and uncommon species.More work is needed to understand how raptor diets vary locally,and the mechanisms that enable exploitation of similar dietary resources.This approach has wide ranging applicability to other birds of prey,and demonstrates the power of using DNA metabarcoding to study species noninvasively.

Source reconstruction for bioluminescence tomography via L_(1/2)regularization

Bioluminescence tomography(BLT)is an important noninvasive optical molecular imaging modality in preclinical research.To improve the image quality,reconstruction algorithms have to deal with the inherent ill-posedness of BLT inverse problem.The sparse characteristic of bioluminescent sources in spatial distribution has been widely explored in BLT and many L1-regularized methods have been investigated due to the sparsity-inducing properties of L1 norm.In this paper,we present a reconstruction method based on L_(1/2) regularization to enhance sparsity of BLT solution and solve the nonconvex L_(1/2) norm problem by converting it to a series of weighted L1 homotopy minimization problems with iteratively updated weights.To assess the performance of the proposed reconstruction algorithm,simulations on a heterogeneous mouse model are designed to compare it with three representative sparse reconstruction algorithms,including the weighted interior-point,L1 homotopy,and the Stagewise Orthogonal Matching Pursuit algorithm.Simulation results show that the proposed method yield stable reconstruction results under different noise levels.Quantitative comparison results demonstrate that the proposed algorithm outperforms the competitor algorithms in location accuracy,multiple-source resolving and image quality.

Performance evaluation of the simpli¯ed spherical harmonics approximation for cone-beam X-ray luminescence computed tomography imaging

As an emerging molecular imaging modality,cone-beam X-ray luminescence computed tomog-raphy(CB-XLCT)uses X-ray-excitable probes to produce near-infrared(NIR)luminescence and then reconst ructs three-dimensional(3D)distribution of the probes from surface measurements.A proper photon-transportation model is critical to accuracy of XLCT.Here,we presented a systematic comparison between the common-used Monte Carlo model and simplified spherical harmonics(SPN).The performance of the two methods was evaluated over several main spec-trums using a known XLCT material.We designed both a global measurement based on the cosine similarity and a locally-averaged relative error,to quantitatively assess these methods.The results show that the SP_(3) could reach a good balance between the modeling accuracy and computational efficiency for all of the tested emission spectrums.Besides,the SP_(1)(which is equivalent to the difusion equation(DE))can be a reasonable alternative model for emission wavelength over 692nm.In vivo experiment further demonstrates the reconstruction perfor-mance of the SP:and DE.This study would provide a valuable guidance for modeling the photon-transportation in CB-XLCT.

Effective and robust approach for fluorescence molecular tomography based on CoSaMP and SP_(3)model

Fluorescence molecular tomography(FMT)allows the detection and quantification of various biological processes in small animals in vrivo,which expands the horizons of pre clinical rescarch and drug development.Eficient three dimensional(3D)reconstruction algorithm is the key to accurate localization and quant ification of fAuorescent target in FMT.In this paper,3D recon-struction of FMT is regarded as a sparse signal recovery problem and the compressive sampling matching pursuit(CoSaMP)algorithm is adopted to obtain greedy recovery of fuorescent sig-nals.Moreover,to reduce the modeling error,the simplified spherical harmonics approximation to the radiative transfer equation(RTE),more specifically SP_(3),is utilized to describe light prop-agation in biological tissues.The performance of the proposed reconstruction method is thor-oughly evaluated by simulations on a 3D digital mouse model by comparing it with three representative greedy methods including orthogonal matching pursuit(OMP),stagewise OMP(StOMP),and regularized OMP(ROMP).The CoSaMP combined with SP_(3)shows an im-provement in reconstruction accuracy and exhibits distinct advantages over the comparative algorithms in multiple targets resolving.Stability analysis suggests that CoSaMP is robust to noise and performs stably with reduction of measurements.The feasibility and reoonstruction accuracy of the proposed method are further validated by phantom experimental data.

Research on the Gender Discrimination Phenomenon and the Primary Cause in English and Chinese Language

In this paper, we conduct research on the gender discrimination phenomenon and the primary cause in English and Chinese language. Language is a social phenomenon, so the restriction of the society but the culture is the foundation of the survival and development of human society cannot leave the culture at the same time. Due to physiological differences, men in the social practice play a more important role than woman burdened with a family. We analyze the gender discrimination phenomenon from different unique perspective to eventually understand the mechanism. In the future, we will combine the literature review to modify our proposed methodology.

Research and Development of Butterfly Microfluidic Gene Chip for 19 Common Pathogenic Microorganisms of Nosocomial Infection

Based on butterfly microfluidic gene chip technology,a method for rapid,accurate and efficient detection of 19 common pathogenic microorganisms of nosocomial infection was established,and a butterfly microfluidic gene chip with high-throughput detection was designed and fabricated.Using constant temperature amplification technology,using the polymerase with chain replacement function to react at constant temperature(65℃)and combined with microfluidic chip technology,primers were designed according to the target genes of 19 pathogenic microorganisms,and a butterfly microfluidic gene chip which can detect 19 common pathogenic microorganisms of nosocomial infection was made to simplify the inspection operation process and verify the sensitivity of the chip.The butterfly microfluidic gene chip can be used for the rapid and efficient detection of 19 common pathogenic microorganisms of nosocomial infection,and provides a new idea for the detection and auxiliary diagnosis of pathogenic microorganisms of nosocomial infection.

Yap methylation-induced FGL1 expression suppresses anti-tumor immunity and promotes tumor progression in KRAS-driven lung adenocarcinoma

Background:Despite significant strides in lung cancer immunotherapy,the response rates for Kirsten rat sarcoma viral oncogene homolog(KRAS)-driven lung adenocarcinoma(LUAD)patients remain limited.Fibrinogen-like protein 1(FGL1)is a newly identified immune checkpoint target,and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients.This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer.Methods:The expression levels of FGL1 and SET1 histone methyltransferase(SET1A)in lung cancer were assessed using public databases and clinical sam-ples.Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models.The effects of FGL1 and Yes-associated protein(Yap)on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry.Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program.Results:Upregulation of FGL1 expression in KRAS-mutated cancer was inversely correlated with the infiltration of CD8^(+)T cells.Mechanistically,KRAS activated extracellular signal-regulated kinase 1/2(ERK1/2),which subsequently phosphorylated SET1A and increased its stability and nuclear localization.SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus,thereby promoting Yap-induced transcription of FGL1 and immune evasion in KRAS-driven LUAD.Notably,dual blockade of programmed cell death-1(PD-1)and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients.Conclusion:FGL1 could be used as a diagnostic biomarker of KRAS-mutated lung cancer,and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.

Credit ratings of Chinese online loan platforms based on factor scores and K-means clustering algorithm

The rapid development of Chinese online loan platforms(OLPs),as well as their risks,has attracted widespread attention,increasing the demand for a complete credit rating mechanism.The present study establishes a credit rating indicator system for 130 mainstream Chinese OLPs that combines 12 quantitative metrics of online loan operations similar to commercial bank credit rating indicators,including platform transaction volume and average expected rate of return.We also consider two qualitative indicators of online loan background,namely platform background and guarantee mode,that reflect Chinese characteristics.Subsequently,a factor analysis was conducted to reduce the 14 indicators dimensions.The loads of the rating indicators in the resulting rotating component matrix were refined into an OLP operation scale factor,fund dispersion factor,security factor,and profitability factor.Finally,a K-means clustering algorithm was employed to cluster the factor scores of each OLP,thereby obtaining credit rating results.The empirical results indicate that the proposed machine learning-based credit rating method effectively provides early warnings of problem platforms,yielding more accurate credit ratings than those provided by two mainstream online loan rating websites in China,namely,Wangdaitianyan and Wangdaizhijia.

基于通用迭代收缩阈值算法的多光谱生物发光断层成像

生物发光断层成像(bioluminescence tomography, BLT)是一种高灵敏非侵入式光学分子成像模态,但近红外光在生物组织中传输的复杂性及表面测量信息的有限性,对BLT光源重建算法提出了较高要求.本文提出了一种基于通用迭代收缩阈值(general iterative shrinkage and threshold,GIST)的BLT重建算法,采用非凸平滑剪切绝对偏差(smoothly clipped absolute deviation, SCAD)惩罚项,并通过迭代求解对非凸惩罚项有解析解的邻近算子问题来获得优化结果.此外,重建中也结合了多光谱测量和收缩可行域策略以降低逆问题的不适定性.为评估该算法的光源定位及多光源辨识能力,本文设计了多组仿真和物理仿体实验,并将GIST与几个典型稀疏重建算法进行了对比.实验结果表明GIST算法在不同光源深度和间隔距离的实验中在中心定位误差方面有较大优势.

香菇HMG-box转录因子lelcrp1基因的功能

【目的】研究香菇(Lentinula edodes) HMG-box转录因子LELCRP1 (Lentinula edodes lignocellulase genes regulation protein 1)在木质纤维素降解相关酶基因表达中的功能与作用。【方法】通过double-joint及同源重组方法构建lelcrp1基因RNAi载体,采用根癌农杆菌介导转化的方法转入香菇异核菌株W1菌丝中,筛选得到RNAi转化子,通过Southern杂交检测插入片段在菌株W1基因组中的拷贝数量。采用荧光定量PCR检测RNAi转化子木质纤维素降解酶基因表达水平变化,并在含有3.5μg/mL潮霉素的MYG平板上测定RNAi转化子的菌丝生长速度。【结果】获得了4个lelcrp1基因表达水平与出发菌株W1相比显著下调6–7倍的RNAi转化子。Southern杂交结果显示,lelcrp1基因RNAi片段已成功整合至香菇菌株W1基因组内,并以单拷贝形式存在。对其中2个RNAi转化子的26个木质纤维素降解酶基因表达水平进行分析,发现其中9个纤维素酶基因、1个半纤维素酶基因、2个辅助酶AA9基因和1个锰过氧化物酶基因的表达水平均表现出明显的下调。平板生长试验表明,RNAi转化子菌丝生长速度均显著慢于出发菌株W1。【结论】通过RNAi技术成功抑制了香菇异核菌株中lelcrp1基因表达水平,并导致部分纤维素及木质素酶基因表达水平相应下调,首次发现HMG-box结构域的转录因子能调控木质纤维素降解相关酶基因表达。

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be studied.Building on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study Xue Bi Jing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi Jing.Collectively, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

Magnetic and microwave absorbing properties of Ce-Co-based alloy powders driven with lanthanum content

The composites of Ce-Co-based alloys doped with La content were fabricated via a vacuum arc melting method.The influences of La addition on microstructure,electromagnetic parameters,magnetic property and microwave absorbing property were measured by the corresponding equipment.The morphology characteristics manifest that all samples display sheet structure,and the average particle size of alloy powders increases with increasing La content The saturation magnetization(MS) decreases with increasing La addition as a whole.The minimum reflection loss(RL) of La0.4Ce1.6Co17 alloy powder about-42.29 dB can be obtained about-42.29 dB at 7.84 GHz with the matching thickness of 1.8 mm,and the corresponding effective bandwidth can achieve about 2.24 GHz.In addition,the minimum RL frequency moves towards a lower frequency region as the La content increases.The minimum RL of La0.3Ce1.7Co17alloy powder is less than-20 dB ranging from 1.2 to 2.4 mm in the whole 4-16 GHz.The maximum bandwidth can reach about 4.88 GHz at the given thickness of 1.2 mm.In general,these all indicate that the La addition is beneficial to improving the microwave absorbing performance in both effective bandwidth and absorption intensity.

Triggering a [2]rotaxane molecular shuttle through hydrogen sulfide

A novel chemically-controlled [2]rotaxane molecular shuttle was successfully designed and synthesized. A H_2 S-responsive bulk barrier was introduced between the two identical recognition stations of the [2]rotaxane to prevent dynamic shuttling of the macrocycle. Upon addition of H_2 S, the complete intramolecular cascade reaction occurs in a controllable manner, resulting in removal of the bulk barrier and the shuttling motion of the macrocycle between the two stations recovers.