Pentatricopeptide repeat(PPR)proteins represent one of the largest protein families in plants and typically localize to organelles like mitochondria and chloroplasts.By contrast,CYTOPLASMLOCALIZED PPR1(OsCPPR1)is a cy...Pentatricopeptide repeat(PPR)proteins represent one of the largest protein families in plants and typically localize to organelles like mitochondria and chloroplasts.By contrast,CYTOPLASMLOCALIZED PPR1(OsCPPR1)is a cytoplasm-localized PPR protein that can degrade OsGOLDENLIKE1(OsGLK1)mRNA in the tapetum of rice anther.However,the mechanism,by which OsCPPR1 recognizes and binds to OsGLK1 transcripts,remains unknown.Through protein structure prediction and macromolecular docking experiments,we observed that distinct PPR motif structures of OsCPPR1 exhibited varying binding efficiencies to OsGLK1 RNA.Moreover,RNA-electrophoretic mobility shift assay experiment demonstrated that the recombinant OsCPPR1 can directly recognize and bind to OsGLK1 mRNA in vitro.This further confirmed that the mutations in the conserved amino acids in each PPR motif resulted in loss of activity,while truncation of OsCPPR1 decreased its binding efficiency.These findings collectively suggest that it may require some co-factors to assist in cleavage,a facet that warrants further exploration in subsequent studies.展开更多
In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic...In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell...BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.展开更多
Hydrophobic Val derivative Schiff base copper(II) complexes and dipeptide (AlaAla, GlyGly) derivative Schiff base copper(II) complexes were introduced into egg white lysozyme. X-ray crystal structure analysis revealed...Hydrophobic Val derivative Schiff base copper(II) complexes and dipeptide (AlaAla, GlyGly) derivative Schiff base copper(II) complexes were introduced into egg white lysozyme. X-ray crystal structure analysis revealed amino acid derivative Schiff base copper(II) complexes were obtained. Herein we discuss primarily on the binding mode of copper(II) of the complexes obtained with egg white lysozyme. The electron density of copper(II) ions was confirmed by X-ray crystal structure analysis. The Val derivative Schiff base copper(II) complex was weakly bound at Arg114 of egg white lysozyme. In other copper(II) complexes, binding of copper(II) ions with dissociated ligands to various residues was observed. The binding sites of copper(II) ions were compared with computational scientific predictions.展开更多
The ability to navigate long distances is essential for many animals to locate shelter,food,and breeding grounds.Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnet...The ability to navigate long distances is essential for many animals to locate shelter,food,and breeding grounds.Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnetic field.A highly conserved ironsulfur cluster assembly protein IscA is proposed as an animal magnetoreceptor(MagR).Iron-sulfur cluster binding is also suggested to play an essential role in MagR magnetism and is thus critical in animal magnetoreception.In the current study,we provide evidence for distinct iron binding and iron-sulfur cluster binding in MagR in pigeons,an avian species that relies on the geomagnetic field for navigation and homing.Pigeon MagR showed significantly higher total iron content from both iron-and ironsulfur binding.Y65 in pigeon MagR was shown to directly mediate mononuclear iron binding,and its mutation abolished iron-binding capacity of the protein.Surprisingly,both iron binding and iron-sulfur binding demonstrated synergistic effects,and thus appear to be integral and indispensable to pigeon MagR magnetism.These results not only extend our current understanding of the origin and complexity of MagR magnetism,but also imply a possible molecular explanation for the huge diversity in animal magnetoreception.展开更多
After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astr...After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.展开更多
With the wide use of three-dimensional woven spacer composites(3DWSCs),the market expects greater mechanical properties from this material.By changing the weft fastening method of the traditional I-shape pile yarns,we...With the wide use of three-dimensional woven spacer composites(3DWSCs),the market expects greater mechanical properties from this material.By changing the weft fastening method of the traditional I-shape pile yarns,we designed three-dimensional woven spacer fabrics(3DWSFs)and 3DWSCs with the weft V-shape to improve the compression performance of traditional 3DWSFs.The effects of weft binding structures,V-pile densities,and V-shaped angle were investigated in this paper.It is found that the compression resistance of 3DWSFs with the weft V-shape is improved compared to that with the weft I-shape,the fabric height recovery rate is as high as 95.7%,and the average elastic recovery rate is 59.39%.When the interlayer pile yarn density is the same,the weft V-shaped and weft I-shaped 3DWSCs have similar flatwise pressure and edgewise pressure performance.The compression properties of the composite improve as the density of the V-pile yarns increases.The flatwise compression load decreases as the V-shaped angle decreases.When the V-shaped angle is 28°and 42°,the latitudinal V-shaped 3DWSCs perform exceptionally well in terms of anti-compression cushioning.The V-shaped weft binding method offers a novel approach to structural design of 3DWSCs.展开更多
Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Method...Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.展开更多
Fidgetin,a microtubule-severing enzyme,regulates neurite outgrowth,axonal regeneration,and cell migration by trimming off the labile domain of microtubule polymers.Because maintenance of the microtubule labile domain ...Fidgetin,a microtubule-severing enzyme,regulates neurite outgrowth,axonal regeneration,and cell migration by trimming off the labile domain of microtubule polymers.Because maintenance of the microtubule labile domain is essential for axon initiation,elongation,and navigation,it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury.In this study,we constructed rat models of spinal cord injury and sciatic nerve injury.Compared with spinal cord injury,we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased,whereas fidgetin decreased after peripheral nerve injury.Depletion of fidgetin enhanced axon regeneration after spinal cord injury,whereas expression level of end binding protein 3(EB3)markedly increased.Next,we performed RNA interference to knockdown EB3 or fidgetin.We found that deletion of EB3 did not change fidgetin expression.Conversely,deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3.Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules.Finally,we deleted EB3 and overexpressed fidgetin.We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3.When fidgetin was deleted,the labile portion of microtubules was elongated,and as a result the length of axons and number of axon branches were increased.These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury.Furthermore,they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.展开更多
Mainly for the problem that the friction force generated by the existing process of bind-ing,fixing and fastening the flexible cable on the satellite is unknown,the friction force analysis and experimental research on...Mainly for the problem that the friction force generated by the existing process of bind-ing,fixing and fastening the flexible cable on the satellite is unknown,the friction force analysis and experimental research on the binding point of the flexible cable are carried out.The equivalent model of the cable bundle bound by nylon cable ties is established,the force on the binding point is analyzed,and the empirical formula for calculating the friction force at the binding point is estab-lished.The formula shows that the friction force is related to the cable bundle diameter,the number of winding cycles of silicone rubber tape,the width of nylon cable ties,and the binding force.The friction force tests of the cable diameter of 5.06 mm,8.02 mm,24.02 mm,38.04 mm under different winding turns of tape were carried out,which was compared with the theoretical calculation value.It is concluded that the calculation accuracy of the theoretical model is more than 95%,which can estimate the actual friction force value accurately.This provides a reference and basis for the theoretical and experimental research on the friction force of the flexible cable binding point on satellite.展开更多
Drug target relationship(DTR)prediction is a rapidly evolving area of research in com-putational drug discovery.Despite recent advances in computational solutions that have overcome the challenges of in vitro and in v...Drug target relationship(DTR)prediction is a rapidly evolving area of research in com-putational drug discovery.Despite recent advances in computational solutions that have overcome the challenges of in vitro and in vivo experiments,most computational methods still focus on binary classification.They ignore the importance of binding affinity,which correctly distinguishes between on-targets and off-targets.In this study,we propose a deep learning model based on the microstruc-ture of compounds and proteins to predict drug-target binding affinity(DTA),which utilizes topo-logical structure information of drug molecules and sequence semantic information of proteins.In this model,graph attention network(GAT)is used to capture the deep features of the compound molecular graph,and bidirectional long short-term memory(BiLSTM)network is used to extract the protein sequence features,and the pharmacological context of DTA is obtained by combining the two.The results show that the proposed model has achieved superior performance in both cor-rectly predicting the value of interaction strength and correctly discriminating the ranking of bind-ing strength compared to the state-of-the-art baselines.A case study experiment on COVID-19 con-firms that the proposed DTA model can be used as an effective pre-screening tool in drug discovery.展开更多
The random forest algorithm was applied to study the nuclear binding energy and charge radius.The regularized root-mean-square of error(RMSE)was proposed to avoid overfitting during the training of random forest.RMSE ...The random forest algorithm was applied to study the nuclear binding energy and charge radius.The regularized root-mean-square of error(RMSE)was proposed to avoid overfitting during the training of random forest.RMSE for nuclides with Z,N>7 is reduced to 0.816 MeV and 0.0200 fm compared with the six-term liquid drop model and a three-term nuclear charge radius formula,respectively.Specific interest is in the possible(sub)shells among the superheavy region,which is important for searching for new elements and the island of stability.The significance of shell features estimated by the so-called shapely additive explanation method suggests(Z,N)=(92,142)and(98,156)as possible subshells indicated by the binding energy.Because the present observed data is far from the N=184 shell,which is suggested by mean-field investigations,its shell effect is not predicted based on present training.The significance analysis of the nuclear charge radius suggests Z=92 and N=136 as possible subshells.The effect is verified by the shell-corrected nuclear charge radius model.展开更多
BACKGROUND Extensive evidence has illustrated the promotive role of integrin binding sialoprotein(IBSP)in the progression of multiple cancers.However,little is known about the functions of IBSP in gastric cancer(GC)pr...BACKGROUND Extensive evidence has illustrated the promotive role of integrin binding sialoprotein(IBSP)in the progression of multiple cancers.However,little is known about the functions of IBSP in gastric cancer(GC)progression.AIM To investigate the mechanism underlying the regulatory effects of IBSP in GC progression,and the relationship between IBSP and cleavage and polyadenylation factor 6(CPSF6)in this process.METHODS The mRNA and protein expression of relevant genes were assessed through realtime quantitative polymerase chain reaction and Western blot,respectively.Cell viability was evaluated by Cell Counting Kit-8 assay.Cell invasion and migration were evaluated by Transwell assay.Pyroptosis was measured by flow cytometry.The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation(RIP)assays.RESULTS IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines.IBSP knockdown suppressed cell proliferation,migration,and invasion but facilitated pyroptosis.In the exploration of the regulatory mechanism of IBSP,potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0.The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma.Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3’-untranslated region of IBSP and regulates its expression.Knockdown of CPSF6 inhibited cell proliferation,migration,and invasion but boosted pyroptosis.Through rescue assays,it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression.CONCLUSION Our study highlighted the vital role of the CPSF6/IBSP axis in GC,suggesting that IBSP might be an effective biotarget for GC treatment.展开更多
Shanxi Tongzhi,written during the reign of Emperor Guangxu in the Qing Dynasty,is a typical example of the printed version of ancient Chinese books.Through the textual research of relevant cultural and historical mate...Shanxi Tongzhi,written during the reign of Emperor Guangxu in the Qing Dynasty,is a typical example of the printed version of ancient Chinese books.Through the textual research of relevant cultural and historical materials,combined with the research on the publishing background and the formal binding system,this paper shows that“Shanxi Tongzhi”during Qing Guangxu has four editions since the original edition was compiled and published in 1892.With development and changes,its content has been continuously deepened and expanded.The version inherits the ancient system and extensive collection,the printing form is rigorous,and the binding is simple and exquisite,which has essential historical research value.At the same time,the traditional and straightforward Chinese-style aesthetics of the ancient printed version of“Shanxi Tongzhi”published during Qing Guangxu has a very high reference value for the exploration and development of the new connotation of the modern book form.展开更多
BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.A...BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.AIM To evaluate whether the M2BPGi value,M2BP,and pre-sarcopenia before radiofrequency ablation(RFA)could be useful recurrence and prognostic markers in patients with early-stage HCC.METHODS In total,160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus(HCV)-positive and HCV-negative.Factors contributing to recurrence and liver-related death,including M2BP,M2BPGi,and skeletal muscle mass index,were statistically analyzed.Eighty-three patients were HCV-positive and 77 were HCV-negative.RESULTS In HCV-positive patients,only des-γ-carboxy-prothrombin≥23 mAU/mL was a significant poor prognostic factor affecting survival after RFA.In HCV-negative patients,M2BPGi≥1.86 cutoff index was significantly associated with tumor recurrence,while M2BP was not.M2BPGi≥1.86 cutoff index(hazard ratio,4.89;95%confidence interval:1.97-12.18;P<0.001)and pre-sarcopenia(hazard ratio,3.34,95%confidence interval:1.19-9.37;P=0.022)were independent significant poor prognostic factors in HCV-negative patients.CONCLUSION In HCV-negative patients with primary HCC treated with RFA,lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period.Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.These factors might be useful recurrence and prognostic markers for early-stage primary HCC.展开更多
This paper first discusses the term'binding'and the concept of 'Binding Theory', and then explains some terms in Binding Theory. It provides examples to further explore the relationships between these ...This paper first discusses the term'binding'and the concept of 'Binding Theory', and then explains some terms in Binding Theory. It provides examples to further explore the relationships between these terms. It also introduces the three Binding Principles and finally shows the most prominent development in Binding Theory.展开更多
The binding energy of the deuteron is estimated from the scalar strong interaction hadron theory SSI. The predicted value is 7.7% lower than the measured value. Existence of a spin 1 dineutron with a binding energy 4/...The binding energy of the deuteron is estimated from the scalar strong interaction hadron theory SSI. The predicted value is 7.7% lower than the measured value. Existence of a spin 1 dineutron with a binding energy 4/5 that of the deuteron or 1.78 MeV is predicted. This is verified by the dineutron, first observed in 2012, in <sup>16</sup>Be decay. No free dineutrons are expected to exist in nature as they can decay into deuterons. These binding energies are limited by short range strong interaction internucleon forces but consist of long range electrostatic energies from quark charges.展开更多
This present study investigated the ability of various soy protein hydrolysates(SPHs)in binding calcium.It was demonstrated that the amount of Ca-bound depended greatly on the SPHs obtained using different proteases,w...This present study investigated the ability of various soy protein hydrolysates(SPHs)in binding calcium.It was demonstrated that the amount of Ca-bound depended greatly on the SPHs obtained using different proteases,which included:neutrase, flavourzyme,protease M and pepsin.The maximum level of Ca-bound(66.9 mg/g)occurred when protease M was used to hydrolyze soy protein.Peptide fragments exhibiting high Ca-binding capacity had molecular weights of either 14.4 or 8-9 kDa.The level of Ca-bound increased linearly with the increment of carboxyl content in SPHs,and further deamidation on SPHs from protease M improved Ca-binding of the hydrolysate.展开更多
Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue ...Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.展开更多
基金the Open Competition Program of Top Ten Critical Priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province,China(Grant No.2022SDZG05)the National Natural Science Foundation of China(Grants Nos.32000457,31871231,and 31921004)+1 种基金the Major Program of Guangdong Basic and Applied Research,China(Grant No.2019B030302006)the Double First-Class Discipline Promotion Project,China(Grant No.2021B10564001).
文摘Pentatricopeptide repeat(PPR)proteins represent one of the largest protein families in plants and typically localize to organelles like mitochondria and chloroplasts.By contrast,CYTOPLASMLOCALIZED PPR1(OsCPPR1)is a cytoplasm-localized PPR protein that can degrade OsGOLDENLIKE1(OsGLK1)mRNA in the tapetum of rice anther.However,the mechanism,by which OsCPPR1 recognizes and binds to OsGLK1 transcripts,remains unknown.Through protein structure prediction and macromolecular docking experiments,we observed that distinct PPR motif structures of OsCPPR1 exhibited varying binding efficiencies to OsGLK1 RNA.Moreover,RNA-electrophoretic mobility shift assay experiment demonstrated that the recombinant OsCPPR1 can directly recognize and bind to OsGLK1 mRNA in vitro.This further confirmed that the mutations in the conserved amino acids in each PPR motif resulted in loss of activity,while truncation of OsCPPR1 decreased its binding efficiency.These findings collectively suggest that it may require some co-factors to assist in cleavage,a facet that warrants further exploration in subsequent studies.
基金The Guangdong Basic and Applied Basic Research Foundation(2022A1515010730)National Natural Science Foundation of China(32001647)+2 种基金National Natural Science Foundation of China(31972022)Financial and moral assistance supported by the Guangdong Basic and Applied Basic Research Foundation(2019A1515011996)111 Project(B17018)。
文摘In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.
基金Tianjin Key Medical Discipline Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.
文摘Hydrophobic Val derivative Schiff base copper(II) complexes and dipeptide (AlaAla, GlyGly) derivative Schiff base copper(II) complexes were introduced into egg white lysozyme. X-ray crystal structure analysis revealed amino acid derivative Schiff base copper(II) complexes were obtained. Herein we discuss primarily on the binding mode of copper(II) of the complexes obtained with egg white lysozyme. The electron density of copper(II) ions was confirmed by X-ray crystal structure analysis. The Val derivative Schiff base copper(II) complex was weakly bound at Arg114 of egg white lysozyme. In other copper(II) complexes, binding of copper(II) ions with dissociated ligands to various residues was observed. The binding sites of copper(II) ions were compared with computational scientific predictions.
基金supported by the National Natural Science Foundation of China(31640001 to C.X.,U21A20148 to X.Z.and C.X.)the Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.)。
文摘The ability to navigate long distances is essential for many animals to locate shelter,food,and breeding grounds.Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnetic field.A highly conserved ironsulfur cluster assembly protein IscA is proposed as an animal magnetoreceptor(MagR).Iron-sulfur cluster binding is also suggested to play an essential role in MagR magnetism and is thus critical in animal magnetoreception.In the current study,we provide evidence for distinct iron binding and iron-sulfur cluster binding in MagR in pigeons,an avian species that relies on the geomagnetic field for navigation and homing.Pigeon MagR showed significantly higher total iron content from both iron-and ironsulfur binding.Y65 in pigeon MagR was shown to directly mediate mononuclear iron binding,and its mutation abolished iron-binding capacity of the protein.Surprisingly,both iron binding and iron-sulfur binding demonstrated synergistic effects,and thus appear to be integral and indispensable to pigeon MagR magnetism.These results not only extend our current understanding of the origin and complexity of MagR magnetism,but also imply a possible molecular explanation for the huge diversity in animal magnetoreception.
基金supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP)the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC)+3 种基金the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC)the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY)the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.
基金Fundamental Research Funds for the Central Universities,China(Nos.2232022D-11 and 22D128102/007)Jiangsu Transformation and Upgrading Funding Program for Industrial and Information Industry,ChinaShanghai Natural Science Foundation of Shanghai Municipal Science and Technology Commission,China(No.20ZR1401600)。
文摘With the wide use of three-dimensional woven spacer composites(3DWSCs),the market expects greater mechanical properties from this material.By changing the weft fastening method of the traditional I-shape pile yarns,we designed three-dimensional woven spacer fabrics(3DWSFs)and 3DWSCs with the weft V-shape to improve the compression performance of traditional 3DWSFs.The effects of weft binding structures,V-pile densities,and V-shaped angle were investigated in this paper.It is found that the compression resistance of 3DWSFs with the weft V-shape is improved compared to that with the weft I-shape,the fabric height recovery rate is as high as 95.7%,and the average elastic recovery rate is 59.39%.When the interlayer pile yarn density is the same,the weft V-shaped and weft I-shaped 3DWSCs have similar flatwise pressure and edgewise pressure performance.The compression properties of the composite improve as the density of the V-pile yarns increases.The flatwise compression load decreases as the V-shaped angle decreases.When the V-shaped angle is 28°and 42°,the latitudinal V-shaped 3DWSCs perform exceptionally well in terms of anti-compression cushioning.The V-shaped weft binding method offers a novel approach to structural design of 3DWSCs.
基金supported by a grant from Department of Animal Biology and Research Center for Bioscience and Biotechnology(RCBB),University of Tabriz(6906).
文摘Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.
基金the National Natural Science Foundation of China,Nos.32070725(to ML),82001295(to RHW),31970412(to YL)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。
文摘Fidgetin,a microtubule-severing enzyme,regulates neurite outgrowth,axonal regeneration,and cell migration by trimming off the labile domain of microtubule polymers.Because maintenance of the microtubule labile domain is essential for axon initiation,elongation,and navigation,it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury.In this study,we constructed rat models of spinal cord injury and sciatic nerve injury.Compared with spinal cord injury,we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased,whereas fidgetin decreased after peripheral nerve injury.Depletion of fidgetin enhanced axon regeneration after spinal cord injury,whereas expression level of end binding protein 3(EB3)markedly increased.Next,we performed RNA interference to knockdown EB3 or fidgetin.We found that deletion of EB3 did not change fidgetin expression.Conversely,deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3.Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules.Finally,we deleted EB3 and overexpressed fidgetin.We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3.When fidgetin was deleted,the labile portion of microtubules was elongated,and as a result the length of axons and number of axon branches were increased.These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury.Furthermore,they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.
基金supported by National Defense Basic Scientific Research Funding Project(No.JCKY2022203C048)Equipment Advanced Research Funding Program(No.41423010401).
文摘Mainly for the problem that the friction force generated by the existing process of bind-ing,fixing and fastening the flexible cable on the satellite is unknown,the friction force analysis and experimental research on the binding point of the flexible cable are carried out.The equivalent model of the cable bundle bound by nylon cable ties is established,the force on the binding point is analyzed,and the empirical formula for calculating the friction force at the binding point is estab-lished.The formula shows that the friction force is related to the cable bundle diameter,the number of winding cycles of silicone rubber tape,the width of nylon cable ties,and the binding force.The friction force tests of the cable diameter of 5.06 mm,8.02 mm,24.02 mm,38.04 mm under different winding turns of tape were carried out,which was compared with the theoretical calculation value.It is concluded that the calculation accuracy of the theoretical model is more than 95%,which can estimate the actual friction force value accurately.This provides a reference and basis for the theoretical and experimental research on the friction force of the flexible cable binding point on satellite.
文摘Drug target relationship(DTR)prediction is a rapidly evolving area of research in com-putational drug discovery.Despite recent advances in computational solutions that have overcome the challenges of in vitro and in vivo experiments,most computational methods still focus on binary classification.They ignore the importance of binding affinity,which correctly distinguishes between on-targets and off-targets.In this study,we propose a deep learning model based on the microstruc-ture of compounds and proteins to predict drug-target binding affinity(DTA),which utilizes topo-logical structure information of drug molecules and sequence semantic information of proteins.In this model,graph attention network(GAT)is used to capture the deep features of the compound molecular graph,and bidirectional long short-term memory(BiLSTM)network is used to extract the protein sequence features,and the pharmacological context of DTA is obtained by combining the two.The results show that the proposed model has achieved superior performance in both cor-rectly predicting the value of interaction strength and correctly discriminating the ranking of bind-ing strength compared to the state-of-the-art baselines.A case study experiment on COVID-19 con-firms that the proposed DTA model can be used as an effective pre-screening tool in drug discovery.
基金Supported by Basic and Applied Basic Research Project of Guangdong Province(2021B0301030006)。
文摘The random forest algorithm was applied to study the nuclear binding energy and charge radius.The regularized root-mean-square of error(RMSE)was proposed to avoid overfitting during the training of random forest.RMSE for nuclides with Z,N>7 is reduced to 0.816 MeV and 0.0200 fm compared with the six-term liquid drop model and a three-term nuclear charge radius formula,respectively.Specific interest is in the possible(sub)shells among the superheavy region,which is important for searching for new elements and the island of stability.The significance of shell features estimated by the so-called shapely additive explanation method suggests(Z,N)=(92,142)and(98,156)as possible subshells indicated by the binding energy.Because the present observed data is far from the N=184 shell,which is suggested by mean-field investigations,its shell effect is not predicted based on present training.The significance analysis of the nuclear charge radius suggests Z=92 and N=136 as possible subshells.The effect is verified by the shell-corrected nuclear charge radius model.
文摘BACKGROUND Extensive evidence has illustrated the promotive role of integrin binding sialoprotein(IBSP)in the progression of multiple cancers.However,little is known about the functions of IBSP in gastric cancer(GC)progression.AIM To investigate the mechanism underlying the regulatory effects of IBSP in GC progression,and the relationship between IBSP and cleavage and polyadenylation factor 6(CPSF6)in this process.METHODS The mRNA and protein expression of relevant genes were assessed through realtime quantitative polymerase chain reaction and Western blot,respectively.Cell viability was evaluated by Cell Counting Kit-8 assay.Cell invasion and migration were evaluated by Transwell assay.Pyroptosis was measured by flow cytometry.The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation(RIP)assays.RESULTS IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines.IBSP knockdown suppressed cell proliferation,migration,and invasion but facilitated pyroptosis.In the exploration of the regulatory mechanism of IBSP,potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0.The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma.Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3’-untranslated region of IBSP and regulates its expression.Knockdown of CPSF6 inhibited cell proliferation,migration,and invasion but boosted pyroptosis.Through rescue assays,it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression.CONCLUSION Our study highlighted the vital role of the CPSF6/IBSP axis in GC,suggesting that IBSP might be an effective biotarget for GC treatment.
文摘Shanxi Tongzhi,written during the reign of Emperor Guangxu in the Qing Dynasty,is a typical example of the printed version of ancient Chinese books.Through the textual research of relevant cultural and historical materials,combined with the research on the publishing background and the formal binding system,this paper shows that“Shanxi Tongzhi”during Qing Guangxu has four editions since the original edition was compiled and published in 1892.With development and changes,its content has been continuously deepened and expanded.The version inherits the ancient system and extensive collection,the printing form is rigorous,and the binding is simple and exquisite,which has essential historical research value.At the same time,the traditional and straightforward Chinese-style aesthetics of the ancient printed version of“Shanxi Tongzhi”published during Qing Guangxu has a very high reference value for the exploration and development of the new connotation of the modern book form.
文摘BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.AIM To evaluate whether the M2BPGi value,M2BP,and pre-sarcopenia before radiofrequency ablation(RFA)could be useful recurrence and prognostic markers in patients with early-stage HCC.METHODS In total,160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus(HCV)-positive and HCV-negative.Factors contributing to recurrence and liver-related death,including M2BP,M2BPGi,and skeletal muscle mass index,were statistically analyzed.Eighty-three patients were HCV-positive and 77 were HCV-negative.RESULTS In HCV-positive patients,only des-γ-carboxy-prothrombin≥23 mAU/mL was a significant poor prognostic factor affecting survival after RFA.In HCV-negative patients,M2BPGi≥1.86 cutoff index was significantly associated with tumor recurrence,while M2BP was not.M2BPGi≥1.86 cutoff index(hazard ratio,4.89;95%confidence interval:1.97-12.18;P<0.001)and pre-sarcopenia(hazard ratio,3.34,95%confidence interval:1.19-9.37;P=0.022)were independent significant poor prognostic factors in HCV-negative patients.CONCLUSION In HCV-negative patients with primary HCC treated with RFA,lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period.Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
文摘This paper first discusses the term'binding'and the concept of 'Binding Theory', and then explains some terms in Binding Theory. It provides examples to further explore the relationships between these terms. It also introduces the three Binding Principles and finally shows the most prominent development in Binding Theory.
文摘The binding energy of the deuteron is estimated from the scalar strong interaction hadron theory SSI. The predicted value is 7.7% lower than the measured value. Existence of a spin 1 dineutron with a binding energy 4/5 that of the deuteron or 1.78 MeV is predicted. This is verified by the dineutron, first observed in 2012, in <sup>16</sup>Be decay. No free dineutrons are expected to exist in nature as they can decay into deuterons. These binding energies are limited by short range strong interaction internucleon forces but consist of long range electrostatic energies from quark charges.
文摘This present study investigated the ability of various soy protein hydrolysates(SPHs)in binding calcium.It was demonstrated that the amount of Ca-bound depended greatly on the SPHs obtained using different proteases,which included:neutrase, flavourzyme,protease M and pepsin.The maximum level of Ca-bound(66.9 mg/g)occurred when protease M was used to hydrolyze soy protein.Peptide fragments exhibiting high Ca-binding capacity had molecular weights of either 14.4 or 8-9 kDa.The level of Ca-bound increased linearly with the increment of carboxyl content in SPHs,and further deamidation on SPHs from protease M improved Ca-binding of the hydrolysate.
基金supported by grants from National Natural Science Foundation of China(81670559)Key Research and Development Project of Shanxi Province(201603D421023)+2 种基金Youth Fund of Shanxi Medical University(02201514)Graduate Student Education Innovation Project of Shanxi(2016BY077)Youth Fund of Ap-plied Basic Research Program of Shanxi(201701D221175)
文摘Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.
