Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson...Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.展开更多
In the process of infecting plants, plant parasitic nematodes release a series of proteins that play an essential role in the successful infection and pathogenesis of plant cells and tissues through stylets or body wa...In the process of infecting plants, plant parasitic nematodes release a series of proteins that play an essential role in the successful infection and pathogenesis of plant cells and tissues through stylets or body walls. In this study,based on transcriptome data, a chorismate mutase gene of Radopholus similis(RsCM) was identified and cloned,which is a single copy gene specifically expressed in the oesophageal gland and highly expressed in juveniles and females. Transient expression of RsCM in tobacco leaves showed that it was localised in the cytoplasm and nucleus of tobacco leaf cells, which inhibited the pattern-triggered immunity(PTI) induced by flg22, including callose deposition and defence gene expression, and cell death induced by immune elicitors BAX, but could not inhibit cell death induced by immune elicitors Gpa2/RBP-1. The RNA interference(RNAi) transgenic tomato of RsCM obviously inhibited the infection, pathogenicity, and reproduction of R. similis. However, the resistance of the overexpression transgenic tomato of RsCM to R. similis infection was significantly reduced, and the expression levels of two salicylic acid(SA) pathway genes(PR1 and PR5) in roots infected by the nematode were significantly down-regulated,which indicated that RsCM might be involved in the inhibition of SA pathway. The results of this study demonstrate that RsCM suppresses the host immune system and might be a new target for the control of R. similis, which also provides new data for the function and mechanism of CM genes of migratory parasitic plant nematodes.展开更多
Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colore...Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colorectal lesions in the Chinese population.Methods This was a multicenter,single-blind,randomized,controlled trial with a non-inferiority design.Patients undergoing endoscopy for physical examination,screening,and surveillance were enrolled from July 2017 to December 2020.The primary outcome measure was the adenoma detection rate(ADR),defined as the proportion of patients with at least one adenoma detected.The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression.Results Out of 653 eligible patients enrolled,data from 596 patients were analyzed.The ADRs were 34.5%in the SD-WL group,33.5%in the HD-WL group,and 37.5%in the HD-NBI group(P=0.72).The advanced neoplasm detection rates(ANDRs)in the three arms were 17.1%,15.5%,and 10.4%(P=0.17).No significant differences were found between the SD group and HD group regarding ADR or ANDR(ADR:34.5%vs.35.6%,P=0.79;ANDR:17.1%vs.13.0%,P=0.16,respectively).Similar results were observed between the HD-WL group and HD-NBI group(ADR:33.5%vs.37.7%,P=0.45;ANDR:15.5%vs.10.4%,P=0.18,respectively).In the univariate and multivariate logistic regression analyses,neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80).Conclusion HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients.It can be concluded that HD-NBI or HD-WL is not superior to SD-WL,but more effective instruction may be needed to guide the selection of different endoscopic methods in the future.Our study’s conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources,especially advanced imaging technologies.展开更多
Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human or...Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.展开更多
Background The prognosis and survival of patients with lung cancer are likely to deteriorate with metastasis.Using deep-learning in the detection of lymph node metastasis can facilitate the noninvasive calculation of ...Background The prognosis and survival of patients with lung cancer are likely to deteriorate with metastasis.Using deep-learning in the detection of lymph node metastasis can facilitate the noninvasive calculation of the likelihood of such metastasis,thereby providing clinicians with crucial information to enhance diagnostic precision and ultimately improve patient survival and prognosis.Methods In total,623 eligible patients were recruited from two medical institutions.Seven deep learning models,namely Alex,GoogLeNet,Resnet18,Resnet101,Vgg16,Vgg19,and MobileNetv3(small),were utilized to extract deep image histological features.The dimensionality of the extracted features was then reduced using the Spearman correlation coefficient(r≥0.9)and Least Absolute Shrinkage and Selection Operator.Eleven machine learning methods,namely Support Vector Machine,K-nearest neighbor,Random Forest,Extra Trees,XGBoost,LightGBM,Naive Bayes,AdaBoost,Gradient Boosting Decision Tree,Linear Regression,and Multilayer Perceptron,were employed to construct classification prediction models for the filtered final features.The diagnostic performances of the models were assessed using various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value.Calibration and decision-curve analyses were also performed.Results The present study demonstrated that using deep radiomic features extracted from Vgg16,in conjunction with a prediction model constructed via a linear regression algorithm,effectively distinguished the status of mediastinal lymph nodes in patients with lung cancer.The performance of the model was evaluated based on various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value,which yielded values of 0.808,0.834,0.851,0.745,0.829,and 0.776,respectively.The validation set of the model was assessed using clinical decision curves,calibration curves,and confusion matrices,which collectively demonstrated the model's stability and accuracy.Conclusion In this study,information on the deep radiomics of Vgg16 was obtained from computed tomography images,and the linear regression method was able to accurately diagnose mediastinal lymph node metastases in patients with lung cancer.展开更多
TToo tthhee eeddiittoorr::Eating disorder(ED),as defined by the Diagnostic and Statistical Manual of Mental Disorders(DSM-5),is a persistent disturbance of eating or eating-related behaviour that results in the altere...TToo tthhee eeddiittoorr::Eating disorder(ED),as defined by the Diagnostic and Statistical Manual of Mental Disorders(DSM-5),is a persistent disturbance of eating or eating-related behaviour that results in the altered consumption or absorption of food and that significantly impairs physical health or psychosocial functioning.^(1)The DSM-5 outlines criteria for EDs,including anorexia nervosa,bulimia nervosa,binge-eating disorder,pica,rumination disorder and avoidant/restrictive food intake disorder.EDs are relatively common in young people,affecting 5.5%-17.9%of young women and 0.6%-2.4%of young men by the time they reach early adulthood.展开更多
Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H ...Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.展开更多
Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategie...Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.展开更多
INTRODUCTION Gender dysphoria(GD),or gender identity disorder,is defined as persistent distress stemming from the incongruence between one's assigned sex at birth and gender identity.'GD has traditionally been...INTRODUCTION Gender dysphoria(GD),or gender identity disorder,is defined as persistent distress stemming from the incongruence between one's assigned sex at birth and gender identity.'GD has traditionally been introduced as a rare condition predominant in assigned males at birth(AMABs).2 However,recent studies have shown an upward trend in assigned females at birth(AFABs)with a dramatic reversal of the AMAB:AFAB ratio-.5-The actual AMAB:AFAB ratio varies by age group and study population.4-Questions have been raised concerning the increasing number of youth who seek professional care for GD,especially adolescent AFABs.展开更多
For the measurement of responsivity of an infrared photodetector,the most-used radiation source is a blackbody.In such a measurement system,distance between the blackbody,the photodetector and the aperture diameter ar...For the measurement of responsivity of an infrared photodetector,the most-used radiation source is a blackbody.In such a measurement system,distance between the blackbody,the photodetector and the aperture diameter are two parameters that contribute most measurement errors.In this work,we describe the configuration of our responsivity measurement system in great detail and present a method to calibrate the distance and aperture diameter.The core of this calibration method is to transfer direct measurements of these two parameters into an extraction procedure by fitting the experiment data to the calculated results.The calibration method is proved experimentally with a commercially extended InGaAs detector at a wide range of blackbody temperature,aperture diameter and distance.Then proof procedures are further extended into a detector fabricated in our laboratory and consistent results were obtained.展开更多
On the basis of the current theoretical understanding of boron-based hard superconductors under ambient conditions,numerous studies have been conducted with the aim of developing superconducting materials with favorab...On the basis of the current theoretical understanding of boron-based hard superconductors under ambient conditions,numerous studies have been conducted with the aim of developing superconducting materials with favorable mechanical properties using boron-rich compounds.In this paper,first-principles calculations reveal the existence of an unprecedented family of tetragonal pentaborides MB_(5)(M=Na,K,Rb,Ca,Sr,Ba,Sc,and Y),comprising B_(20)cages and centered metal atoms acting as stabilizers and electron donors to the boron sublattice.These compounds exhibit both superconductivity and high hardness,with the maximum superconducting transition temperature T_(c)of 18.6 K being achieved in RbB5 and the peak Vickers hardness Hv of 35.1 GPa being achieved in KB_(5)at 1 atm.The combination of these properties is particularly evident in KB_(5),RbB5,and BaB5,with Tc values of∼14.7,18.6,and 16.3 K and H_(v)values of∼35.1,32.4,and 33.8 GPa,respectively.The results presented here reveal that pentaborides can provide a framework for exploring and designing novel superconducting materials with favorable hardness at achievable pressures and even under ambient conditions.展开更多
Self-incompatibility(SI)is a kind of plant fertilization obstacle,which can prevent the harmful effects of inbreeding decline,but it hinders the breeding of inbred lines.Tea plants have SI and long-term cross-pollinat...Self-incompatibility(SI)is a kind of plant fertilization obstacle,which can prevent the harmful effects of inbreeding decline,but it hinders the breeding of inbred lines.Tea plants have SI and long-term cross-pollination,which limits the progress of genetic research and variety improvement.However,the mechanism of SI in tea plants is still a mystery.Herein,microscopic observation showed that the pollen tube could pass through the base of style and enter the ovary cavity after 48 h of self-pollination at different flowering stages,and the SI intensity at bud stage and full bloom stage was lower than initial bloom stage.RNA-seq analysis showed that 1,463 and 1,409 differentially expressed genes(DEGs)were associated with low SI at bud stage and full bloom stage,respectively,and 507 DEGs were associated with SI at initial bloom stage.The results of qRT-PCR validation of 20 DEGs were consistent with the RNA-seq data.Furthermore,CsRNS,CsSRKL5 and CsSRKL8 specifically expressed in style,which may be related to the low SI at bud stage,and three CsACC genes may be related to the low SI at full bloom stage.The results provide useful information for understanding the mechanism of SI in tea plants.展开更多
AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.展开更多
Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "fac...Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.展开更多
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteob...Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.展开更多
文摘Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.
基金funded by the Guangdong Basic and Applied Basic Research Foundation,China(2021A1515011273)he National Natural Science Foundation of China(31071665)。
文摘In the process of infecting plants, plant parasitic nematodes release a series of proteins that play an essential role in the successful infection and pathogenesis of plant cells and tissues through stylets or body walls. In this study,based on transcriptome data, a chorismate mutase gene of Radopholus similis(RsCM) was identified and cloned,which is a single copy gene specifically expressed in the oesophageal gland and highly expressed in juveniles and females. Transient expression of RsCM in tobacco leaves showed that it was localised in the cytoplasm and nucleus of tobacco leaf cells, which inhibited the pattern-triggered immunity(PTI) induced by flg22, including callose deposition and defence gene expression, and cell death induced by immune elicitors BAX, but could not inhibit cell death induced by immune elicitors Gpa2/RBP-1. The RNA interference(RNAi) transgenic tomato of RsCM obviously inhibited the infection, pathogenicity, and reproduction of R. similis. However, the resistance of the overexpression transgenic tomato of RsCM to R. similis infection was significantly reduced, and the expression levels of two salicylic acid(SA) pathway genes(PR1 and PR5) in roots infected by the nematode were significantly down-regulated,which indicated that RsCM might be involved in the inhibition of SA pathway. The results of this study demonstrate that RsCM suppresses the host immune system and might be a new target for the control of R. similis, which also provides new data for the function and mechanism of CM genes of migratory parasitic plant nematodes.
基金supported by the Beijing Municipal Science and Technology Commission(BMSTC,No.D171100002617001).
文摘Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colorectal lesions in the Chinese population.Methods This was a multicenter,single-blind,randomized,controlled trial with a non-inferiority design.Patients undergoing endoscopy for physical examination,screening,and surveillance were enrolled from July 2017 to December 2020.The primary outcome measure was the adenoma detection rate(ADR),defined as the proportion of patients with at least one adenoma detected.The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression.Results Out of 653 eligible patients enrolled,data from 596 patients were analyzed.The ADRs were 34.5%in the SD-WL group,33.5%in the HD-WL group,and 37.5%in the HD-NBI group(P=0.72).The advanced neoplasm detection rates(ANDRs)in the three arms were 17.1%,15.5%,and 10.4%(P=0.17).No significant differences were found between the SD group and HD group regarding ADR or ANDR(ADR:34.5%vs.35.6%,P=0.79;ANDR:17.1%vs.13.0%,P=0.16,respectively).Similar results were observed between the HD-WL group and HD-NBI group(ADR:33.5%vs.37.7%,P=0.45;ANDR:15.5%vs.10.4%,P=0.18,respectively).In the univariate and multivariate logistic regression analyses,neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80).Conclusion HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients.It can be concluded that HD-NBI or HD-WL is not superior to SD-WL,but more effective instruction may be needed to guide the selection of different endoscopic methods in the future.Our study’s conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources,especially advanced imaging technologies.
基金This work was supported by the National Natural Science Foundation of China(Nos.81874496,82374530)the Clinical Medical Technology Innovation Guide Project of Hunan Province(No.2020SK53206)+3 种基金the Natural Science Foundation of Hunan Province(No.2021JJ70062)the Changsha Natural Science Foundation Project(No.kq2014019)the Health Special Fund Research Project of Hunan Province(No.B2020-07)the Clinical Pharmaceutical Research Fund of Hunan Medical Association(No.B202012).
文摘Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.
基金the Science and Technology Funding Project of Hunan Province,China(2023JJ50410)(HX)Key Laboratory of Tumor Precision Medicine,Hunan colleges and Universities Project(2019-379)(QL).
文摘Background The prognosis and survival of patients with lung cancer are likely to deteriorate with metastasis.Using deep-learning in the detection of lymph node metastasis can facilitate the noninvasive calculation of the likelihood of such metastasis,thereby providing clinicians with crucial information to enhance diagnostic precision and ultimately improve patient survival and prognosis.Methods In total,623 eligible patients were recruited from two medical institutions.Seven deep learning models,namely Alex,GoogLeNet,Resnet18,Resnet101,Vgg16,Vgg19,and MobileNetv3(small),were utilized to extract deep image histological features.The dimensionality of the extracted features was then reduced using the Spearman correlation coefficient(r≥0.9)and Least Absolute Shrinkage and Selection Operator.Eleven machine learning methods,namely Support Vector Machine,K-nearest neighbor,Random Forest,Extra Trees,XGBoost,LightGBM,Naive Bayes,AdaBoost,Gradient Boosting Decision Tree,Linear Regression,and Multilayer Perceptron,were employed to construct classification prediction models for the filtered final features.The diagnostic performances of the models were assessed using various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value.Calibration and decision-curve analyses were also performed.Results The present study demonstrated that using deep radiomic features extracted from Vgg16,in conjunction with a prediction model constructed via a linear regression algorithm,effectively distinguished the status of mediastinal lymph nodes in patients with lung cancer.The performance of the model was evaluated based on various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value,which yielded values of 0.808,0.834,0.851,0.745,0.829,and 0.776,respectively.The validation set of the model was assessed using clinical decision curves,calibration curves,and confusion matrices,which collectively demonstrated the model's stability and accuracy.Conclusion In this study,information on the deep radiomics of Vgg16 was obtained from computed tomography images,and the linear regression method was able to accurately diagnose mediastinal lymph node metastases in patients with lung cancer.
基金Funding Effort for some personnel was supported by grants K12 DA041449(KYX,PI:Laura Bierut,Patricia Cavazos-Rehg),and the American Psychiatric Association Psychiatric Research Fellowship(KYX).Authors BYL and C-FS were American Psychiatric Association(APA)/APA Foundation(APAF)fellows at the time of publication.Research grant funding received from Gilead Pharmaceuticals,Liva Nova Therapeutics,Curemark and Alto Neuroscience(ASK).
文摘TToo tthhee eeddiittoorr::Eating disorder(ED),as defined by the Diagnostic and Statistical Manual of Mental Disorders(DSM-5),is a persistent disturbance of eating or eating-related behaviour that results in the altered consumption or absorption of food and that significantly impairs physical health or psychosocial functioning.^(1)The DSM-5 outlines criteria for EDs,including anorexia nervosa,bulimia nervosa,binge-eating disorder,pica,rumination disorder and avoidant/restrictive food intake disorder.EDs are relatively common in young people,affecting 5.5%-17.9%of young women and 0.6%-2.4%of young men by the time they reach early adulthood.
基金supported by the National Natural Science Foundation of China (Grant Nos.81874006,82172399,81902222,82060395,81902277,82072504,82000845)the Hunan Province Natural Science Foundation of China (Grant Nos.2020JJ4928,2020JJ4897,2021JJ30038,2021JJ40492)the Independent Exploration and Innovation Project of Central South University (Grant Nos.2020zzts255)。
文摘Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
基金This work was partly supported by grant from the Youth Fund of National Natural Science Foundation of China(81800441)Start-up Fund from Shanghai Fourth People’s Hospital Affiliated to Tongji University,Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center,Construction and Application of Emergency and Critical Care Integrated Management Mode(SHDC22021211).
文摘Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.
基金supported in part by the National Key Research and Development Program of China(2018YFB1304903)in part by the National Natural Science Foundation of China(62003116,61925304,and 62127810)+1 种基金in part by the Project funded by China Postdoctoral Science Foundation(2021M690832)in part by the Heilongjiang Postdoctoral Fund of China(LBH-Z20138)。
文摘本文介绍了一种基于磁驱动正交悬臂探针(magnetically driven-orthogonal cantilever probes,MDOCP)的三维原子力显微镜(three-dimensional atomic force microscopy,3D-AFM)表征方法,该方法采用两个独立的三自由度纳米扫描器,能够实现探针沿可控矢量角度跟踪扫描样品表面。该3D-AFM系统还配备了高精度旋转台,可实现360°全向成像。定制的MD-OCP包含水平悬臂、垂直悬臂和磁球三部分,其中磁球可在磁场中机械驱动OCP实现激振。垂直悬臂具有一个突出的尖端,可检测深槽和具有悬垂/凹边特征的结构。首先,对MD-OCP的设计、模拟、制造和性能分析进行了描述;其次,详细介绍了探针振幅补偿和360°旋转原点定位的方法。通过使用标准AFM阶梯光栅进行对比实验,验证了所提出方法对于陡峭侧壁和拐角处细节的表征能力,其中采用了三维地形重建方法将图像整合。通过对具有微梳结构的微机电系统(MEMS)器件进行3D表征,进一步证实了所提出基于MD-OCP的3D-AFM技术的有效性。最后,该技术被用于确定微阵列芯片的关键尺寸(critical dimensions,CD)。实验结果表明,所提出的方法可以高精度地获取三维结构的CD信息,相比于难以获得侧壁信息的二维技术,在三维微纳制造检测领域具有更好的潜力。
文摘INTRODUCTION Gender dysphoria(GD),or gender identity disorder,is defined as persistent distress stemming from the incongruence between one's assigned sex at birth and gender identity.'GD has traditionally been introduced as a rare condition predominant in assigned males at birth(AMABs).2 However,recent studies have shown an upward trend in assigned females at birth(AFABs)with a dramatic reversal of the AMAB:AFAB ratio-.5-The actual AMAB:AFAB ratio varies by age group and study population.4-Questions have been raised concerning the increasing number of youth who seek professional care for GD,especially adolescent AFABs.
基金This work was supported by the National Key Technologies R&D Program of China(No.2019YFA0705203,2019YFA070104)the National Natural Science Foundation of China(No.62004189)the State Key Laboratory of Special Rare Metal Materials,Northwest Rare Metal Materials Research Institute(No.SKL2023K00X).
文摘For the measurement of responsivity of an infrared photodetector,the most-used radiation source is a blackbody.In such a measurement system,distance between the blackbody,the photodetector and the aperture diameter are two parameters that contribute most measurement errors.In this work,we describe the configuration of our responsivity measurement system in great detail and present a method to calibrate the distance and aperture diameter.The core of this calibration method is to transfer direct measurements of these two parameters into an extraction procedure by fitting the experiment data to the calculated results.The calibration method is proved experimentally with a commercially extended InGaAs detector at a wide range of blackbody temperature,aperture diameter and distance.Then proof procedures are further extended into a detector fabricated in our laboratory and consistent results were obtained.
基金supported by the National Natural Science Foundation of China(Grant Nos.12104127 and 22131006)the Doctoral Starting Up Foundation of Hebei Normal University for Nationalities(Grant No.DR2020001)+1 种基金the Clean Energy(Carbon Peaking and Carbon Neutrality)Industry Research Institute of Chengde(Grant No.202205B090)the Natural Science Foundation of Shandong Province(Grant No.ZR2020QA060)。
文摘On the basis of the current theoretical understanding of boron-based hard superconductors under ambient conditions,numerous studies have been conducted with the aim of developing superconducting materials with favorable mechanical properties using boron-rich compounds.In this paper,first-principles calculations reveal the existence of an unprecedented family of tetragonal pentaborides MB_(5)(M=Na,K,Rb,Ca,Sr,Ba,Sc,and Y),comprising B_(20)cages and centered metal atoms acting as stabilizers and electron donors to the boron sublattice.These compounds exhibit both superconductivity and high hardness,with the maximum superconducting transition temperature T_(c)of 18.6 K being achieved in RbB5 and the peak Vickers hardness Hv of 35.1 GPa being achieved in KB_(5)at 1 atm.The combination of these properties is particularly evident in KB_(5),RbB5,and BaB5,with Tc values of∼14.7,18.6,and 16.3 K and H_(v)values of∼35.1,32.4,and 33.8 GPa,respectively.The results presented here reveal that pentaborides can provide a framework for exploring and designing novel superconducting materials with favorable hardness at achievable pressures and even under ambient conditions.
基金supported by the Project of Major Science and Technology in Anhui Province(202003a06020021)the Project of Innovation and Training of Anhui Agricultural University(XJDC2021084)the National Natural Science Foundation of China(U20A2045).
文摘Self-incompatibility(SI)is a kind of plant fertilization obstacle,which can prevent the harmful effects of inbreeding decline,but it hinders the breeding of inbred lines.Tea plants have SI and long-term cross-pollination,which limits the progress of genetic research and variety improvement.However,the mechanism of SI in tea plants is still a mystery.Herein,microscopic observation showed that the pollen tube could pass through the base of style and enter the ovary cavity after 48 h of self-pollination at different flowering stages,and the SI intensity at bud stage and full bloom stage was lower than initial bloom stage.RNA-seq analysis showed that 1,463 and 1,409 differentially expressed genes(DEGs)were associated with low SI at bud stage and full bloom stage,respectively,and 507 DEGs were associated with SI at initial bloom stage.The results of qRT-PCR validation of 20 DEGs were consistent with the RNA-seq data.Furthermore,CsRNS,CsSRKL5 and CsSRKL8 specifically expressed in style,which may be related to the low SI at bud stage,and three CsACC genes may be related to the low SI at full bloom stage.The results provide useful information for understanding the mechanism of SI in tea plants.
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.
基金supported by the National Natural Science Foundation of China (Grant nos. 81522012, 81702237, 81670807, 81871822, 81801395, 81600699, 81701383, and 81802138)the Thousand Youth Talents Plan of China (Grant no. D1119003)+8 种基金the Medicine and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences (Grant no. 2018-I2M-HL-024)the High Level Talent Gathering Project of Hunan Province (Grant nos. 2017XK2039, and 2018RS3029)the Innovation Driven Project of Central South University (Grant nos. 2016CX028,2019CX014, and 2018CX029)the Youth Foundation of Xiangya Hospital in Central South University (Grant no. 2016Q10)the Hunan Provincial Innovation Foundation for Postgraduate (Grant no. CX2018B045)the Fundamental Research Funds for the Central Universities of Central South University (Grant nos. 2017zzts211 and 2018zzts895)the Hunan Province Natural Science Foundation of China (Grant no. 2017JJ3501)the China Postdoctoral Science Foundation (Grant nos. 2017M612596, 2017M622614, and 2018M632998)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province (Grant no. 2016A030306051)
文摘Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
基金provided by K01-AR060433 (T.Q.)K08-AR064833 (J.C)R01-AR063943 (X.C)
文摘Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.
