A theoretical study of the signal enhancement mechanism of coaxial DP-LIBS

In the field of dual-pulse laser-induced breakdown spectroscopy(DP-LIBS)research,the pursuit of methods for determining pulse intervals and other parameters quickly and conveniently in order to achieve optimal spectral signal enhancement is paramount.To aid researchers in identification of optimal signal enhancement conditions and more accurate interpretation of the underlying signal enhancement mechanisms,theoretical simulations of the spatiotemporal processes of coaxial DP-LIBS-induced plasma have been established in this work.Using a model based on laser ablation and two-dimensional axisymmetric fluid dynamics,plasma evolutions during aluminum–magnesium alloy laser ablation under single-pulse and coaxial dualpulse excitations have been simulated.The influences of factors,such as delay time,laser fluence,plasma temperature,and particle number density,on the DP-LIBS spectral signals are investigated.Under pulse intervals ranging from 50 to 1500 ns,the time evolutions of spectral line intensity,dual-pulse emission enhancement relative to the single-pulse results,laser irradiance,spatial distribution of plasma temperature and species number density,as well as laser irradiance shielded by plasma have been obtained.The study indicates that the main reason behind the radiation signal enhancement in coaxial DP-LIBS-induced plasma is attributed to the increased species number density and plasma temperature caused by the second laser,and it is inferred that the shielding effect of the plasma mainly occurs in the boundary layer of the stagnation point flow over the target surface.This research provides a theoretical basis for experimental research,parameter optimization,and signal enhancement tracing in DP-LIBS.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation mechanism, functional crosstalk, and signaling addiction

The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor over- expression, generation of structure-defected variants, and point mutations in the kinase domain contribute to RON signaling activation. Recently, functional crosstalk between RON and signaling proteins such as MET and EFGR has emerged as an additional mechanism for RON activation, which is critical for tumorigenic develop- ment. The RON signaling crosstalk acts either as a regulatory feedback loop that strengthens or enhances tumor- igenic phenotype of cancer cells or serves as a signaling compensatory pathway providing a growth/survival ad- vantage for cancer cells to escape targeted therapy. Moreover, viral oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into cellular signaling network essential for cancer cell growth and survival. These activities provide the mo- lecular basis of targeting RON for cancer treatment. In this review, we will discuss recent data that uncover the mechanisms of RON activation in cancer cells, review evidence of RON signaling crosstalk relevant to cancer malignancy, and emphasize the significance of the RON signaling addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling will not only provide insight into the mechanisms of tumor pathogenesis, but also lead to the development of novel strategies for molecularly targeted cancer treatment.

Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer

Colorectal cancer is the second most leading cause of cancer related deaths in the western countries. One of the forms of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC), also known as "Lynch syndrome". It is the most common hereditary form of cancer accounting for 5%-10% of all colon cancers. HNPCC is a dominant autosomal genetic disorder caused by germ line mutations in mismatch repair genes. Human mismatch repair genes play a crucial role in genetic stability of DNA, the inactivation of which results in an increased rate of mutation and often a loss of mismatch repair function. Recent studies have shown that certain mismatch repair genes are involved in the regulation of key cellular processes including apoptosis. Thus, differential expression of mismatch repair genes particularly the contributions of MLH1 and MSH2 play important roles in therapeutic resistance to certain cytotoxic drugs such as cisplatin that is used normally as chemoprevention. An understanding of the role of mismatch repair genes in molecular signaling mechanism of apoptosis and its involvement in HNPCC needs attention for further work into this important area of cancer research, and this review article is intended to accomplish that goal of linkage of apoptosis with HNPCC. The current review was not intended to provide a comprehensive enumeration of the entire body of literature in the area of HNPCC or mismatch repair system or apoptosis; it is rather intended to focus primarily on the current state of knowledge of the role of mismatch repair proteins in molecular signaling mechanism of apoptosis as it relates to understanding of HNPCC.

Computational and bioinformatics tools for understanding disease mechanisms

Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.

Stress release mechanism of deep bottom hole rock by ultra-high-pressure water jet slotting

To solve the problems of rock strength increase caused by high in-situ stress,the stress release method with rock slot in the bottom hole by an ultra-high-pressure water jet is proposed.The stress conditions of bottom hole rock,before and after slotting are analyzed and the stress release mechanism of slotting is clarified.The results show that the stress release by slotting is due to the coupling of three factors:the relief of horizontal stress,the stress concentration zone distancing away from the cutting face,and the increase of pore pressure caused by rock mass expansion;The stress concentration increases the effective stress of rock along the radial distance from O.6R to 1R(R is the radius of the well),and the presence of groove completely releases the stress,it also allows the stress concentration zone to be pushed away from the cutting face,while significantly lowering the value of stresses in the area the drilling bit acting,the maximum stress release efficiency can reach 80%.The effect of slotting characteristics on release efficiency is obvious when the groove location is near the borehole wall.With the increase of groove depth,the stress release efficiency is significantly increased,and the release range of effective stress is enlarged along the axial direction.Therefore,the stress release method and results of simulations in this paper have a guiding significance for best-improving rock-breaking efficiency and further understanding the technique.

Sinusoidal FM Fuze's Channel Leak and Its Jamming Mechanism

Aim To get the theory base of designing FM fuze's jamming signal, its jamming mechanism was studied. Methods A sinusoidal FM fuze was analyzed in time domain and frequency domain and the concept of channel leak was presented. Results It was proved that information channel leak exists in FM fuze because of the nonlinear property of the mixer. The jamming signal was designed based on the channel leak and the jamming mechanism was analyzed in detail. Conclusion This kind of jamming signal can jam the sinusoidal FM fuzes effectively just depending on the jamming signal's feature itself. It's different from the traditional jamming way of simulating echo. Though the sinusoidal FM fuze was just analyzed, the principle is applicable to all FM fuzes. At the same time, it may be used as the reference for FM radar and communication countermeasures.

针对传感节点的基于signal-slot电源管理方案设计与实现

随着传感网络和3G网络的融合,物联网已经成为新世纪最重要的技术之一,如何延长传感节点的工作时间已成为物联网研究的一个重要课题。传统的电源管理规范如APM(Advanced Power Management)和ACPI(Advanced Configuration and Power Interface)主要针对PC设计,因其复杂性和对BIOS层要求等因素,在无线传感节点中并不适用。为了解决此问题,针对传感节点计算和存储能力有限的特点,我们首先开发了精简的signalslot框架,基于signal-slot框架,并设计了简单有效的电源管理方案SPM(Simple Power Management),并将SPM在流行的传感节点操作系统Contiki中实现。

Therapeutic potential and mechanism of functional oligosaccharides in inflammatory bowel disease: a review

Inflammatory bowel disease(IBD)is characterized by recurrent attacks and long courses,and the number of patients has expanded rapidly year by year.Additionally,current conventional strategies exist serious adverse effects.In this case,it is an urgent issue to find out an effective and safe treatment.Functional oligosaccharides possess safe and excellent physiological activities,and have attracted enormous attention due to their great therapeutic potential for IBD.This review emphasizes the attenuating effects of distinct functional oligosaccharides on IBD and their structure,and summarizes the main mechanisms from the aspects of regulating intestinal fl ora structure,repairing intestinal barrier,modulating immune function and mediating related signaling pathways in order to reveal the relationship between functional oligosaccharides,immune regulation,intestinal epithelial cells,gut fl ora and IBD treatment.Oligosaccharides possess excellent protective effects on IBD,and can be considered as safe and functional ingredients in the health food and pharmaceutical industry.

Recent Advances on Early-Stage Fire-Warning Systems: Mechanism, Performance, and Perspective

Early-stage fire-warning systems(EFWSs)have attracted significant attention owing to their superiority in detecting fire situations occurring in the pre-combustion process.Substantial progress on EFWSs has been achieved recently,and they have presented a considerable possibility for more evacuation time to control constant unintentional fire hazards in our daily life.This review mainly makes a comprehensive summary of the current EFWSs,including the working mechanisms and their performance.According to the different working mechanisms,fire alarms can be classified into graphene oxide-based fire alarms,semiconductor-based fire alarms,thermoelectric-based fire alarms,and fire alarms on other working mechanisms.Finally,the challenge and prospect for EFWSs are briefly provided by comparing the art of state of fire alarms.This work can propose a more comprehensive understanding of EFWSs and a guideline for the cutting-edge development direction of EFWSs for readers.

Role of TGF-βl Signaling in Heart Valve Calcification Induced by Abnormal Mechanical Stimulation in a Tissue Engineering Model

A tissue engineering model of heart valve calcification induced in a bio-reactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms.Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs)were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and three-leaflet tissue engineered valves.The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A),low (1000mL/min,group B),medium (2000mL/min,group C),and high velocity (3000mL/min,group D)for 14 days. Morphology and calcification were assessed by yon Kossa staining,alkaline phosphatase (ALP)content,and Runx2 immunostaining.Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-β1,bone morphogenetic protein 2 (BMP2),Smadl,and MSX2 were measured at different time points.ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions.The results showed that during 14 days of flow stimulation,huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A,B,and C.Under mechanical stimulation,huVICs showed a parallel growth pattern in the direction of the fluid flow,but huVICs exhibited disordered growth in the high-velocity flow environment,yon Kossa staining,ALP measurement,and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D.Expression levels of TGF-β1,BMP2, and MSX2 mRNA and protein were increased under fluid stimulation.ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced.In conclusion,abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model.The extent of calcification correlated positively with the flow velocity,as did the mRNA and protein levels of TGF-β1,BMP2,and MSX2.These findings indicate that TGF-β1/BMP2 signaling is involved in valve calcification induced bv abnormal mechanical stimulation.

Mechanisms of ductular reaction in non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease(NAFLD)is a disease spectrum caused in part by insulin resistance and genetic predisposition.This disease is primarily characterized by excessive lipid accumulation in hepatocytes in the absence of alcohol abuse and other causes of liver damage.Histologically,NAFLD is divided into several periods:simple steatosis,non-alcoholic steatohepatitis(NASH),hepatic fibrosis,cirrhosis,and hepatocellular carcinoma.With the increasing prevalence of obesity and hyperlipidemia,NAFLD has become the main cause of chronic liver disease worldwide.As a result,the pathogenesis of this disease is drawing increasing attention.Ductular reaction(DR)is a reactive bile duct hyperplasia caused by liver injury that involves hepatocytes,cholangiocytes,and hepatic progenitor cells.Recently,DR is shown to play a pivotal role in simple steatosis progression to NASH or liver fibrosis,providing new research and treatment options.This study reviews several DR signaling pathways,including Notch,Hippo/YAP-TAZ,Wnt/β-catenin,Hedgehog,HGF/c-Met,and TWEAK/Fn14,and their role in the occurrence and development of NASH.

Transcriptomic analysis reveals putative osmoregulation mechanisms in the kidney of euryhaline turbot Scophthalmus maximus responded to hypo-saline seawater

Turbot harbor a relatively remarkable ability to adapt to opposing osmotic challenges and are an excellent model species to study the physiological adaptations of flounder associated with osmoregulatory plasticity.The kidney transcriptome of turbot treated 24 h in water of hypo-salinity(salinity 5)and seawater(salinity 30)was sequenced and characterized.In silico analysis indicated that all unigenes had significant hits in seven databases.The functional annotation analysis of the transcriptome showed that the immune system and biological processes associated with digestion,absorption,and metabolism played an important role in the osmoregulation of turbot in response to hypo-salinity.Analysis of biological processes associated with inorganic channels and transporters indicated that mineral absorption and bile secretion contributed to iono-osmoregulation resulting in cell volume regulation and cell phenotypic plasticity.Moreover,we analyzed and predicted the mechanisms of canonical signaling transduction.Biological processes involved in renin secretion,ECM-receptor interaction,adherens junction,and focal adhesion played an important role in the plasticity phenotype in hypo-stress,while the signal transduction network composed of the MAPK signaling pathway and PI3K-Akt signaling pathway with GABAergic synapse,worked in hypoosmoregulation signal transduction in the turbot.In addition,analysis of the tissue specificity of targeted gene expression using qPCR during salinity stress was carried out.The results showed that the kidney,gill,and spleen were vital regulating organs of osmotic pressure,and the osmoregulation pattern of euryhaline fish dif fered among species.

A Review on the Protection Mechanism of Trehalose on Plant Tissues and Animal Cells

Trehalose is a non-reducing disaccharide composed of glucose molecules connected byα-glycosidic bond.This soluble substance plays an important role of protecting green algae and other lower plants from stress.It can help plants cope with extreme environments such as severe cold,drought and high salinity,regulate the stomatal conductance and water utilization rate of plants,and participate in the growth and metabolism regulation of plants as a signal molecule.As an impermeable cryoprotectant,trehalose is widely used in the refrigeration protection of various animal cells and tissues due to its non-toxicity and high efficiency.According to the research results at home and abroad in recent years,the protection,regulation and mechanism of trehalose on plant tissues and animal cells were summarized,so as to provide a theoretical basis for the further development and utilization of trehalose.

EEG Emotion Recognition Using an Attention Mechanism Based on an Optimized Hybrid Model

Emotions serve various functions.The traditional emotion recognition methods are based primarily on readily accessible facial expressions,gestures,and voice signals.However,it is often challenging to ensure that these non-physical signals are valid and reliable in practical applications.Electroencephalogram(EEG)signals are more successful than other signal recognition methods in recognizing these characteristics in real-time since they are difficult to camouflage.Although EEG signals are commonly used in current emotional recognition research,the accuracy is low when using traditional methods.Therefore,this study presented an optimized hybrid pattern with an attention mechanism(FFT_CLA)for EEG emotional recognition.First,the EEG signal was processed via the fast fourier transform(FFT),after which the convolutional neural network(CNN),long short-term memory(LSTM),and CNN-LSTM-attention(CLA)methods were used to extract and classify the EEG features.Finally,the experiments compared and analyzed the recognition results obtained via three DEAP dataset models,namely FFT_CNN,FFT_LSTM,and FFT_CLA.The final experimental results indicated that the recognition rates of the FFT_CNN,FFT_LSTM,and FFT_CLA models within the DEAP dataset were 87.39%,88.30%,and 92.38%,respectively.The FFT_CLA model improved the accuracy of EEG emotion recognition and used the attention mechanism to address the often-ignored importance of different channels and samples when extracting EEG features.

A Multi-View Gait Recognition Method Using Deep Convolutional Neural Network and Channel Attention Mechanism

In many existing multi-view gait recognition methods based on images or video sequences,gait sequences are usually used to superimpose and synthesize images and construct energy-like template.However,information may be lost during the process of compositing image and capture EMG signals.Errors and the recognition accuracy may be introduced and affected respectively by some factors such as period detection.To better solve the problems,a multi-view gait recognition method using deep convolutional neural network and channel attention mechanism is proposed.Firstly,the sliding time window method is used to capture EMG signals.Then,the back-propagation learning algorithm is used to train each layer of convolution,which improves the learning ability of the convolutional neural network.Finally,the channel attention mechanism is integrated into the neural network,which will improve the ability of expressing gait features.And a classifier is used to classify gait.As can be shown from experimental results on two public datasets,OULP and CASIA-B,the recognition rate of the proposed method can be achieved at 88.44%and 97.25%respectively.As can be shown from the comparative experimental results,the proposed method has better recognition effect than several other newer convolutional neural network methods.Therefore,the combination of convolutional neural network and channel attention mechanism is of great value for gait recognition.

Negatively regulating mechanism of Sirpal in hepatocellular carcinoma:an experimental study

BACKGROUND: Signal regulatory protein ( Sirp) is a recently isolated, cloned and identified inhibitor receptor distributed in the membrane of hematopoietic and nonhema-topoietic cells. Sirp alphal ( Sirpα1) is a member of Sirp families. Sirpal can bind SHP-2 in the form of tyrosine phosphorylation by SH2 effect and negatively regulate growth factor, oncogene, or insulin-induced responses as its substrate. This study aimed to preliminarily clarify the negatively regulating proliferation mechanism of Sirpal in liver cancer. METHODS: pLXSN, Sirpα1 and Sirpα1Δ4Y2 plasmids were respectively transfected into Sk-Hepl liver cancer cell line, and various stable Sk-Hepl cell lines were obtained with screening agent of G418 (1200 μg/ml). The expressing levels of cyclin D1, CDK4, Fas, β-catenin and gankyrin in various cell lines were determined with Western blotting. Cell cycles were determined at 0, 12 and 24 hours with flow cytotnetry after various synchronous cell lines were cultured without serum for 72. Cell apoptosis induced with agent of TNF-α (50 ng/ml) was determined with flow cytotnetry at 0,0.5,1,3,6 and 12 hours. RESULTS: Sirpα1 could significantly decrease the expression of cyclin D1, β-catenin and gankyrin, but it couldn't affect the expression level of CDK4 and Fas. When synchronous cells were cultured for 12 hours, S phase Sk-Hep1 cell transfected with Sirpal plasmid was the lowest [(31.92 ± 0.22)% vs. other cell lines, P <0.05], and the cell line was highly sensitive to TNF-α agent for 1 hour. (59.31 ±0.59)% of apoptotic cells occurred (vs. the other time points, P < 0.05). CONCLUSIONS: Sirpal might block the cell cycle of liver cancer, inhibit cell proliferation, promote cell apoptosis by decreasing the expression of cyclin D1, β-catenin and gankyrin. It is one of the important mechanisms inhibiting the occurrence and development of hepatocellular carcinoma.

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

Perlecan/Hspg2 Deficiency Impairs Bone’s Calcium Signaling and Associated Transcriptome in Response to Mechanical Loading

Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and attenuates loading4nduced bone formation in perlecan deficient mice(Hypo).Considering that intracellular calcium[Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction,we hypothesized that perlecan deficiency impairs bone’s calcium signaling in response to loading.To test this,we performed real-time[Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading(8 N,Figure 1).Relative to wild type(WT),Hypo osteocytes showed decreases in the overall[Ca2+]i response rate(-58%),calcium peaks(-33%),cells with multiple peaks(-53%),peak magnitude(-6.8%),and recovery speed to baseline(-23%).RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling,ECM-receptor interaction,and focal adhesion pathways following repetitive loading.Defects in the endoplasmic reticulum(ER)calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Sercal calcium pumps were identified in Hypo bones.Taken together,impaired calcium signaling may contribute to bone’s reduced anabolic response to loading,underlying the osteoporosis risk for the SJS patients.