The objective of this study was to investigate the significance of portal vein reconstruction in segment IV of the liver on early postoperative liver function recovery in split liver transplantation. The clinical data of patients of right trilobe split liver transplantation in our center were analyzed and divided into two groups, including a group without portal vein reconstruction and a group with portal vein reconstruction. Clinical data of alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (ALB), creatinine (Cr), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl Transferase (GGT), lactic acid (Lac), and international normalized ratio (INR) levels were analyzed. The technique of segment IV portal vein reconstruction is beneficial to the early postoperative recovery of liver function. Statistically, there was no significant effect of portal vein reconstruction in the IV segment of the liver on the recovery of liver function within 1 week after split liver transplantation. There was no significant difference in survival rate between the control group and reconstruction group over the 6 months follow-up period after surgery.  Since the first liver transplant was performed, with the continuous advancement of surgical techniques, extensive development, and clinical application of various new immunosuppressants, liver transplantation has become the most effective means of treating various end-stage liver diseases . SuccessThere is no statistically significant difference in the graft and recipient survival rates at 1 year for those who have had whole liver transplantation and those who have undergone adult split liver transplantation , 6. In ein situ split techniques for the fabrication of split grafts acceptable for two adult patients. In order to enhance the arterial supply to segment IV, they retain the common portal vein and the common hepatic duct with the right graft and the celiac axis with the left graft  Indications for liver transplantation with no contraindications; 2) preoperative Model for end-stage liver disease (MELD) score <30 points; 3) GrafOf 32 patients, those who did not undergo portal vein reconstruction were included in the control group, consisting of 14 cases in total, and the 18 patients who underwent portal vein reconstruction were included in the reconstruction group. From the first to seventh days after the operation, ALT, AST, albumin (ALB), creatinine (Cr), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl Transferase (GGT), lactic acid (Lac), and international normalized ratio (INR) level data were collected to analyze the significance of portal vein reconstruction of donor liver segment IV in patients with early postoperative liver function recovery.t-test was used for independent samples. The reconstruction group was compared with the control group. Data with a p-value of less than 0.05 were considered statistically significant.STATA statistical software was used for data processing, normally distributed measurement data were expressed as mean ± standard deviation, and There was a statistically significant difference between the control and reconstruction groups in the levels of ALT on days 2, 4, 5, 6, and 7 after surgery, and in the levels of Lac on day 1 after surgery, but there was no statistically significant difference in AST, ALB, Cr, TB, ALP, GGT, and INR as determined by a comparison of data which is shown in Judging from the recovery of various indicators of the recipients in the two groups after surgery, the recovery of liver function in the reconstruction group was significantly better than that in the control group. No serious bleeding, biliary fistula, or other complications occurred in the two groups of recipients after operation. In the control group, 14 recipients did not undergo segment IV hepatic portal vein reconstruction, and the segment IV liver was insufficiently perfused. Ultrasonography indicated that segment IV liver atrophy and necrosis occurred earlier, and early postoperative liver function recovery was poor. The postoperative ultrasound of the 18 recipients in the reconstruction group showed blood flow through the reconstructed vessels of the portal vein in the recipients within 1 week after surgery, the speed of IV segment liver atrophy was significantly slower than that of the control group, and the postoperative liver function recovered faster. It can be seen that intraoperative reconstruction of the portal vein of the donor liver segment IV can effectively reduce the damage of hepatocytes, preserve more functional liver tissue, and promote the early postoperative liver function recovery of patients, thereby improving the prognosis of patients and restoring blood recirculation, which is shown in We compared the 6-month data to calculate the survival rate between these two groups.The 6-month rate in the Control group and Reconstruction group was [85.7% vs. 94.4%] with an overall 90.6% rate of survival. There was no significant difference in survival rate between these two groups is shown in the The development of split liver transplant was prompted by a lack of organs and rising morbidity on waiting lists. The gap between organ supply and recipient demand has never been wider than it is today. This has rekindled interest in expanding the use of traditional adult/pediatric split liver transplant and adult/adult split liver transplant. At centers that routinely use these techniques, split liver transplant applied to pediatric recipients offers good results, with considerable decreases in pediatric wait times, wait-list morbidity, and living-donation utilization, according to a decade of experience with left lateral segment grafts , 21. Splin situ split liver transplantation in our center was controlled at more than 1.0%, and there was no obvious small liver syndrome after operation. We believe that the hyperoxia environment of the transplanted liver is beneficial to the regeneration of liver cells.The recipient selection of donation after brainstem death (DBD) orthotopic split liver transplantation is also key to the success of the transplantation, especially when the recipient is a double adult split liver transplantation. The matching degree between the graft size and the recipient needs to be carefully evaluated before operation to prevent the possibility of small for size syndrome or large for size syndrome due to the mismatch between the donor and the recipient. The GRWR standard of DBD orthotopic split liver transplantation should be appropriately increased compared with living donor liver transplantation, and it is recommended to be greater than 1.0%–1.2% . The GRWin situ splitting in vivo compared with the traditional in vitro splitting after acquisition, it can significantly reduce the cold ischemia time, dissect the hilar tissue more finely, deal with the liver section more accurately, and reduce the incidence of postoperative complications. It is suggested that the middle hepatic vein should be accurately located by intraoperative ultrasound before splitting, and perfusion can be carried out after splitting when the middle hepatic vein is exposed (Therefore, the receptor should be emphasized to ensure long-term oxygen inhalation after operation. CT examination involves radiation and may affect the regeneration of liver cells. Therefore, we suggest that abdominal CT examination should be avoided as much as possible in the early stage after operation. Split liver transplantation is complex, the operation time is relatively increased, there are risks such as cross-sectional bile leakage and infection after operation, and the general requirements for the recipient are high because relevant studies show that a high MELD score before operation is an independent risk factor for serious complications after liver transplantation, so care should be taken to select recipients with a MELD score >14 for split liver transplantation , 18, 25. exposed .Although the vascular reconstruction and repair molding of the left and right liver halves respectively increase the operation time, it ensures that the left and right liver grafts have a complete middle hepatic vein system, the operation method is more reasonable, the necrosis of the graft liver tissue caused by outflow tract obstruction is avoided, and the functional liver volume of the graft is effectively increased. After the blood supply of the donor liver is restored during the operation, the sections of each anastomosis and liver parenchyma are comprehensively checked, and the bleeding points and broken ends with bile leakage are also treated in time. The reconstruction of the artery is flexibly evaluated according to the distribution of the donor hepatic artery and the recipient’s own arterial conditions. If the length of the vessel is not sufficient, the donor iliac vessel can be used for bridging if necessary. In general, T-tube drainage is routinely placed in our center. The advantages of T-tube drainage are as follows: first, the recovery of donor liver function and the occurrence of rejection can be evaluated by observing the amount and color of drained bile in the early stage after operation; The second is that it can fulfil the role of biliary decompression before the recovery of gastrointestinal function, so as to reduce the occurrence of biliary complications such as bile leakage.In conclusion, split liver transplantation can effectively alleviate the problem of liver shortages. Split liver transplantation can give the same clinical results as whole liver transplantation if the right donors and recipients are chosen and if the surgery is planned and carried out well. With the continuous maturity and progress of split liver transplantation technology, split liver transplantation is expected to become a routine operation in clinical liver transplantation and to become widely used. To sum up, our center’s exploration of portal vein reconstruction in segment IV of the liver in split liver transplantation is a reasonable attempt based on anatomy, which is conducive to the recovery of patient’s early postoperative liver function in clinical practice. However, because this surgical method is in the early exploratory stage, the number of samples included in this study is limited and, due to the differences in the technical level of the operators, the results have certain limitations that need to be further verified by continuing to expand the sample size in a multi-center practice.


Plasmodium falciparum is the most lethal parasite of its genus but has evaded many treatment and vaccine efforts due to its complex life cycle and redundant invasion mechanisms. Epitope-based vaccines hold significant promise for malaria vaccine development due to their ease of development and ability to target dominant regions in antigenically variable pathogens. The recently characterized protein P. falciparum merozoite Rh5 interacting protein (PfRipr) is nonredundant, highly conserved, and essential for erythrocyte invasion, making it an ideal target for a bloodstage malaria vaccine.Malaria infections remain an enormous contributor to global fatalities with an estimated death toll of 619,000 in 2021 and 77% of deaths being children aged under 5 years. Transmitted via mosquito, Merozoite InvasionModel of binding and insertion of PRCR complex to erythrocyte basigin in merozoite invasion. Adapted from Scally et al. 2022.P. falciparum sequences collected from Burkina Faso and Uganda, we assessed the immunogenic potential of PfRipr epitopes with regard to T-cell receptor binding and B-cell recognition. T-cell receptor binding was predicted using NetMHCpan searching against MHC I and II alleles with high regional frequencies. Using an in-silico 3D model of PfRipr predicted via AlphaFold, tertiary structures of all PfRipr sample sequences were predicted via SWISS-MODEL then analyzed by ElliPro to identify linear and discontinuous B-cell epitopes. Putative epitopes were filtered using allele coverage, conservation, antigenicity, and allergenicity.Using B-Cell Epitope PredictionProtocol for B-cell epitope prediction using AlphaFold for template modeling, Swiss-Model for homology-based modeling of sample sequences, and ElliPro for continuous and discontinuous epitope prediction.Epitope Sorting and FilteringProtocol for sorting T-cell epitopes using Average Allele Coverage  and B-cell epitopes using ElliPro Score (Protrusion Index representing surface accessibility of the epitope).P. falciparum.Between the two datasets, there were 19 matching epitopes with 7 MHC I, 9 MHC II, 1 linear, and 2 discontinuous. These epitopes were used to design a multi-epitope-based bloodstage vaccine construct against MHC EpitopesPartial list of MHC epitopes found in Burkina Faso and Uganda datasets.B-Cell EpitopesB-cell epitopes found in Burkina Faso and Uganda datasets.PfRipr 3D Structure with B-cell Epitopes3D model of PfRipr predicted via AlphaFold with labeled B-cell epitopesin silico protein stabilization and docking simulations, in vitro methods such as HLA stabilization or T-cell activation assays, and in vivo methods using transgenic mouse models. The pipeline of immunoinformatic analyses formulated in this project can be further applied to P. falciparum sequence datasets collected from other malaria endemic regions to develop vaccines effective against circulating strains.To validate their predicted immunogenicity, epitopes can be further investigated using Multi-Epitope Vaccine ConstructSchematic representation of hypothetical multi-epitope vaccine construct. FliC is added to the N-terminus to stimulate and amplify immune response. The EAAAK linker is used to separate the bifunctional fusion protein domains. AAY linkers are used to amplify MHC I and II epitopes and prevent junctional epitope binding. GPGPG linkers between B-cell epitopes function to minimize junctional epitopes and retain conformational-dependent immunogenicity. A six amino acid Histidine (6H) chain was added to the C-terminus to aid during lab purification processes.All Authors: No reported disclosures


This research aimed to characterize the physicochemical, in vitro digestion, and structural features of digestion residues of maize and sorghum starches subjected to thermoplastic extrusion, along with the influence of Sodium Stearoyl Lactylate (SSL), to obtain improved starches for food applications and to understand their behavior when consumed as a food ingredient. The morphology of the extruded materials showed remanent starch granules when SSL was used. A higher amount of medium and large linear glucan chains were found in these particles, influencing higher thermal stability (ΔH ≈ 4 J/g) and a residual crystallinity arrangement varying from 7 to 17% in the extrudates. Such structural features were correlated with their digestibility, where slowly digestible starch (SDS) and resistant starch (RS) fractions ranged widely . By analyzing the data with a Principal component analysis (PCA), we found strong influences of B2 and B3 type chains on the thermal stability of the extrudates. The amylose and smaller glucan chains (A and B1) also significantly affected the emulsifying and foam stability properties. This research contributes to the molecular knowledge of starch in extruded products with broad food applications. Moreover, the extrusion cooking of maize starch at a screw speed of 125 rpm yielded more amylose–lipid complexes. Other investigations have tested emulsifiers aimed to retard staling on intermediate-moisture bread due to molecular interactions with starch, enabling single helical V-type complexes with amylose, reducing starch swelling and amylose leaching, avoiding migration of water from gluten, and diminishing starch crystallization [Starch is one of the most abundant polysaccharides in nature and is crucial for human nutrition. Practically all over the globe, starch-rich foods and ingredients constitute the main staples for humankind, cereals being one of the most used sources for its isolation . Industrlization . This colization . Complimlization  evaluatelization ,9, and tMaize and sorghum starch were provided by Cervecería Cuauhtemoc Moctezuma, Heineken’s subsidiary in Mexico. Sodium Stearoyl Lactylate (SSL) was provided by Paalsgard . All other reagents were laboratory grade.All analyses were performed in triplicate.Native corn starch was extruded using a twin-screw corotating extruder  with a 600 mm length and L/D = 20 at a volumetric feed rate of 4 kg/h . The die diameter was 5 mm, and the screw configuration was selected specifically to create high levels of shear. The first section contained only conveying elements, with the next containing conveying and kneading elements. Finally, the high-shear section contained conveying, reverse conveying, and kneading elements. The temperature was controlled at the final stage of the extruding chamber by using a TT-137 N water heater . The variables where feedstock tempering moisture , temperature , screw speed , and SSL content  .In the case of sorghum starch, we consider reducing the experimental runs due to our preliminary data, which showed close similarities with maize; in this case, the screw speed was fixed at 140 RPM, and the variables tempering moisture: 20% or 40%; temperature: 80 °C or 100 °C; %SSL: 0.5% or 1% were used . Before Starch granules’ morphology and birefringence patterns were observed under normal and polarized light with an Olympus CX-33 microscope  equipped with polarized filters. The images were recorded at 40× magnification.Total starch (K-TSTA) and amylose (K-AMYL) contents were determined using Megazyme kits  using 500 mg of sample, according to the method reported by de la Rosa-Millan et al. . The totAll samples were analyzed with a differential scanning calorimeter , using the conditions and procedure described by de La Rosa-Millán et al. . The onsThe diffraction patterns of starches were obtained using an Advance D8 diffractometer  at 35 kV with a CuK-α radiation source (1.542 Å). The samples were scanned in the angular range of 4–35° (2Ɵ). The crystallinity percentage (%C) was determined from the diffractograms calculating the area corresponding to the crystalline peaks (Ap); from the difference between the area under the curve and the area of the amorphous halo, the total area under the curve (At), and the instrumental noise (N) according to Equation (2)All samples’ in vitro digestion fractions were determined according to the Englyst, Kingman and Cummings  protocolThe method described by Goñi, García-Alonso and Saura-Calixto  was empl2) according to the protocol described by Tetchi, Rolland-Sabaté, Amani, and Colonna [Gel clarity was assessed by the method suggested by de la Rosa-Millan . Briefly Colonna  using a g for 5 min and calculated according to Equation (7).The method described by Pedroche, Yust, Lqari, Girón-Calle, Alaiz, Vioque, and Millán  with sliES) was measured in the previously emulsified tubes heated at 80 °C in a water bath for 30 min, followed by centrifugation at 1300× g for 5 min. Their heat stability was calculated as follows (Equation (8)):Emulsion stability (FC) was estimated in a dispersion of 500 mg of starch in 50 mL of de-ionized water. The pH of the dispersion was adjusted to pH 7.0 with either 1M NaOH or 1N HCL, followed by an Ultra Turrax homogenizer  at 10,000 rpm for 2 min. After the whipped solution was transferred into a 100 mL graduated cylinder, and their volume was recorded and compared with a similar dispersion without stirring, FC was expressed as the increased volume (%) due to stirring, using the following equation (Equation (9)):Foaming capacity (FS) was calculated as the difference in volume (%) of the whipped starch dispersion after 30 min of standing (at ≈ 25 °C). The foam stability was then calculated using the following equation (Equation (10)).The foam stability . Starch samples were prepared as described by Yoo and Jane . The HPSThe debranching of the starch was carried out according to the procedure described by Ao, Simsek, Zhang, Venkatachalam, Reuhs, and Hamaker , using 1All experiments and procedures described in this research were performed in triplicate unless otherwise specified. A one-way variance analysis was performed, and when significant differences were found at the significance level of 0.05, a Tukey test of multiple comparisons was used. Additionally, a Principal component analysis was performed to explain the effect of the molecular composition and interactions. All data were analyzed using the Minitab software .The addition of SSL promoted a dilution effect on the starch content, but no significant differences were detected when extrusion was used. . This beWhen thermal treatments, such as extrusion, are applied to starches, several changes in the crystalline structure occur, affecting their granular characteristics and functionality. Such changes often result in improved water absorption due to newly exposed –OH groups and the partial or total disruption of crystallites due to the depolymerization of amylose chains and amylopectin clusters, evidenced by lower thermal transition intervals (Tf-To) and lower viscosity . For thiWe evaluated the starch digestion fractions to understand how SSL and extrusion conditions impact their digestion. The RDS fraction significantly increased due to the extrusion conditions, from 60% to 75% for maize and from 62% to 72% for sorghum. The SDS fraction decreased from 22.27% to ≈18% in native maize. Meanwhile, the RS fraction increased from 1.2% to 21.41%; this variability could be related to the changes in the molecular structure where molecular weight, starch chain length, and amylopectin crystalline polymorphism influenced this behavior ,16. In sp < 0.05) after extrusion and was further enhanced with SSL   A. Other  sorghum B. Regard sorghum C. These PCA analyses helped understand the extent of molecular interactions within samples, which otherwise would be complicated to explain. We choose the variables related to the starch architecture, in vitro digestibility, and functional properties. The first and second components (PC1 and PC2) accounted for an accumulative variance of 85.4%. The score plot showed significant differences when extrusion with and without SSL was tested, differentiating between starch sources A. The loBoth cereal starches presented similar crystalline characteristics that changed after extrusion. The use of SSL impacts their starch functionality as emulsifiers, foam promoters, and stabilizers by improving their molecular interactions. The influence of amylopectin’s fine molecular structure was relevant since linear glucans, particularly B2 and B3 chains, helped to stabilize the emulsions and generate stable foams, possibly by a molecular interaction mechanism. Enzyme hydrolysis was affected by the molecular composition of starches, promoting differences in the digestion rate that was correlated with the amylopectin crystalline structure, particularly B3 type chains, as well as the resulting long glucans related to amylose. This research’s outcome and potential applications would be useful for developing new food ingredients with broad applications without chemical derivatization.


Sa 1.6 μm, the maximum relative errors are 2.56%, 157.9%, 134%, and 90.3%, respectively. When roughness is Sa 3.2 μm, the maximum relative errors are 2.92%, 152.4%, 108.4%, and 75.1%, respectively. When roughness is Sa 4.5 μm, the maximum relative errors are 2.89%, 158.07%, 68.4%, and 46.13%, respectively. When roughness is Sa 5.8 μm, the maximum relative errors are 2.89%, 201.57%, 110.26%, and 73.18%, respectively. The comparison results demonstrate that the suggested model is accurate. This new method for examining the contact characteristics of mechanical joint surfaces uses the proposed model in conjunction with a micro-topography examination of an actual machined surface.The analytical results of normal contact stiffness for mechanical joint surfaces are quite different from the experimental data. So, this paper proposes an analytical model based on parabolic cylindrical asperity that considers the micro-topography of machined surfaces and how they were made. First, the topography of a machined surface was considered. Then, the parabolic cylindrical asperity and Gaussian distribution were used to create a hypothetical surface that better matches the real topography. Second, based on the hypothetical surface, the relationship between indentation depth and contact force in the elastic, elastoplastic, and plastic deformation intervals of the asperity was recalculated, and the theoretical analytical model of normal contact stiffness was obtained. Finally, an experimental test platform was then constructed, and the numerical simulation results were compared with the experimental results. At the same time, the numerical simulation results of the proposed model, the J. A. Greenwood and J. B. P. Williamson (GW) model, the W. R. Chang, I. Etsion, and D. B. Bogy (CEB) model, and the L. Kogut and I. Etsion (KE) model were compared with the experimental results. The results show that when roughness is  The contact stiffness of mechanical joint surfaces plays an important role in the stability of mechanical systems . Due to Research on the stiffness of the whole machine system must start from the normal contact stiffness of the mechanical joint surfaces. The analysis methods of contact stiffness mainly include the statistical analysis method and the fractal analysis method. The study of contact stiffness based on the statistical analysis method was first initiated by the GW model proposed by Greenwood and Williamson  in 1966.Wang  establis2 + GX + H is established. Based on this hypothetical surface, the relationship between the contact parameters and contact force in the contact area is deduced by the theory of statistics and contact mechanics. Then, a type of contact model that is more suitable for cutting rough surfaces is established. The innovation point of this paper is to establish a parabolic cylindrical asperity model with a cross-sectional contour by analyzing the combined surfaces obtained by various machining methods. Compared with other models, this new model is closer to real contact conditions, and the comparison between experimental results and simulation results shows that the accuracy of this model is very high. The new model is obtained by summarizing all types of binding surface and has a wider application.Research on mechanical joint surfaces should be based on actual topography; otherwise, the normal contact stiffness will be separated from the actual working condition. There is a certain gap between the hypothetical surface and the actual surface, or, to some extent, it can only be close to a certain type of rough surface. There is a great difference between actual topography under different machining methods and spherical or elliptic asperity assumptions, such as turning, milling, and grinding. As a result, there is still no universal model for a wide range of applications. In this paper, based on surface-topography data of various machining methods, a hypothetical surface that can more accurately represent the topography characteristics of an actual cutting surface was established. Therefore, a hypothetical surface of asperities with a cross-sectional profile of parabola Y = CXFrom a microscopic perspective, contact of mechanical joint surfaces is the contact of the asperities on rough surfaces. Therefore, a contact model should be studied from the perspective of asperity contact. In this section, data for rough surfaces will be collected using a white-light interferometer, and the contour parameters of a single asperity will be fitted by combining the topography data measured. Then, according to the above fitting data, a new hypothetical surface will be established.Sa 3.031 μm, Sa 2.418 μm, Sa 0.076 μm, and Sa 0.037 μm, respectively.To obtain actual topography data of rough surfaces, a 3D white-light interferometer  was used to measure the surface topography of workpieces. The device adopts the principle of non-contact white-light interference, closed-loop feedback piezoelectric ceramic, and a high linear capacitance sensor, which can ensure the full range of a 0–150 μm 0.1 nm high-precision test, to ensure the real validity of the test results. As shown in 2 +GX + H was used to fit the data points of a single asperity profile, and the fitting root-means-square error was 0.0002667.The following is a discussion of the shape of a single asperity. A data-fitting method is adopted to process randomly selected single-asperity-measured data points. It can be seen from the fitting results that the parabolic curve can be completely consistent with the measured profile data of the asperity. Therefore, based on the more accurate fitting of the rough-surface topography, the parabolic cylinder is used to represent the shape of the single asperity. The height distribution of asperities is represented by a Gaussian distribution.In summary, based on the analysis of the micro-topography of machined surfaces, a hypothetical surface based on parabolic cylindrical asperity was proposed for the mechanical joint surface in this paper. A single surface asperity is represented by a parabolic column shape, and the height distribution of the asperities is Gaussian. The established hypothetical surface is shown in 2 + GX + H cylinder contact, and the cross angle of the main axis of the cylinder is 45° on average; (2) the curvature radius of all asperity surfaces on the contact surface is the same, and the height of asperity surfaces follows a Gaussian distribution; (3) the deformation of asperities is independent of each other, and the interaction between asperities is ignored in the contact process; (4) only the asperities deform, while the matrix does not participate in deformation; (5) the asperities are uniformly distributed on the matrix. In Based on the contact model established above, this section first analyzes the stress and deformation of two separate asperities in contact with each other. The theoretical formula between the contact force and deformation is solved, and the theoretical normal contact stiffness is obtained. Combined with statistical theory, contact force and deformation formulae for the whole mechanical joint surface were derived, and then a theoretical analytical model of the normal contact stiffness of the whole joint surface was obtained.The contact process of an asperity will undergo three stages: elastic deformation, elastoplastic deformation, and complete plastic deformation. The following will be a separate analysis of the different deformation stages.Elastic deformation2 +GX + H is an elliptic region, and the short diameter a and long diameter b of the ellipse are calculated by Equations (1) and (2) [F is the concentrated force; ν1 and ν2 are the Poisson’s ratios of materials, respectively; and E1 and E2 are the elastic moduli of materials, respectively. The influence coefficients A and B of the principal curvature can be obtained by Equations (3) and (4) [R1 and R1ʹ are object 1 at the contact points of the two main curvature radii, respectively; R2 and R2ʹ are object 2 at the contact points of the two main curvature radii, respectively; φ is the angle between the planes where the two main curvature radii R1 and R2 are located. It is assumed that the contact of two rough surfaces is the contact of two parabolic cylindrical asperities with the same radius of curvature. The mean value of the intersection angle φ of the axes of two asperities is φ = 45°. The radius of curvature at a point on the curve is reciprocal to the curvature of the curve at that point. The radial radii R1 and R2 of the main curvatures of the asperity are equal to the curvature radius R of the parabola, and their curvatures 1/R1 and 1/R2 are also equal: that is, 1/R1 = 1/R2 = 1/R. The axial main radii of curvatures R1ʹ and R2ʹ to infinity obtain curvatures 1/R1ʹ and 1/R2ʹ that are equal to zero; that is, 1/R1ʹ = 1/R2ʹ = 0. By combining Equations (3) and (4), we can obtain B2 +GX + H according to the curvature formula, as shown in Equation (5).According to the Hertz contact theory, the contact surface of two parabolic cylinders Y = CX and (2) .(1)a=α[ and (4) .(3)B+A=Meanwhile, the radius of the main curvature can be determined according to Equation (5).It is assumed that only elastic deformation occurs when two asperities are first in contact. According to the Hertz contact theory, the relationship between proximity distance ω and force F of the center of two asperities can be obtained.οθ = 45° and then consulting the elastic force manually to obtain α = 1.926, β = 0.604, and λ = 1.709.Equation (7)  is the eF at the stage of pure elastic deformation is derived from Equation (8):The relationship between connection displacement ω and force Contact stiffness is the derivative of the contact force concerning displacement. Thus, contact stiffness in the pure-elastic-contact stage can be expressed as:2.Elastoplastic deformationaP = 0.4 H, an asperity on the joint surface begins to yield and deform, thus:H is material hardness. By substituting Equations (1) and (2) into Equation (11), we obtain:According to the contact mechanics theory of Tabor , when thThe force at the onset of plastic deformation of the asperity is obtained after the end of displacement:ω1 at the onset of plastic deformation of the asperity is derived:Then displacement According to the literature , the conAverage contact pressure during elastoplastic deformation is:Thus, the contact force at the elastoplastic deformation stage is obtained:So,Contact stiffness is the derivative of contact force with respect to displacement. Thus, the expression of contact stiffness in the elastic–plastic contact stage can be obtained as follows:2 = 110 ω1.According to the literature , when de3.Complete plastic deformationAccording to the viewpoints of Abbott and Firestone , the relaP = H, the asperity begins to yield completely.According to the contact mechanics theory of Tabor , when thContact stiffness is the derivative of the contact force concerning displacement. Thus, the expression of contact stiffness at the stage of complete plastic deformation is:Based on the analysis in l, and take the average height line of asperities on the lower rough surface as the origin of the z-axis. All asperities with height z is h = z − d. Therefore, the probability of contact at any given height of a rough surface can be obtained from the equation below.When upper and lower rough surfaces contact, assume that the distance between the average height line of asperities on the two rough surfaces is N, then the number of asperities participating in the contact is:If the total number of asperities on the entire contact surface is ω = 2 h = 2(z − d), the total force F can be derived.Meanwhile, since Meanwhile, the total contact stiffness can be obtained by the following equation.The following derivation is made based on the contact stiffness of the joint surface at different deformation stages.Elastic deformationThe expression of the force at the elastic deformation stage is:The expression of contact stiffness at the elastic deformation stage is:2.Elastoplastic deformationThe expression of the contact force at the elastoplastic deformation stage is:The expression of contact stiffness at the elastoplastic deformation stage is3.Complete plastic deformationThe expression of the force at the stage of complete plastic deformation is:The contact stiffness at the stage of complete plastic deformation can be expressed as:E1 = E2 = 209 GPa, Poisson’s ratio ν1 = ν2 = 0.269, hardness H = 1970 MPa) are obtained by conventional mechanical experiments. As shown in Sa 1.6μm, Sa 3.2 μm, Sa 4.5 μm, Sa 5.8 μm; and each roughness has four diameters of 10 mm, 20 mm, 30 mm, and 40 mm. The lower specimen has a diameter of 40 mm. So that the upper and lower roughness specimens are consistent, the lathe and turning tool for each type of roughness specimen are consistent, and the machine tool’s spindle speed, turning angle, feed speed, and turning amount are all consistent. To ensure consistent roughness on the upper and lower specimens, the lathe and turning tools are consistent for each roughness specimen, and the spindle speed, turning angle, feed speed, and turning amount of the machine tool are all consistent.The experimental specimen is made of 45 steel (Carbon (C) content is 0.42~0.50%; Si content is 0.17–0.37%; Mn content is 0.50~0.80%; Cr content is ≤0.25%; Ni content is ≤ 0.30%; Cu content is ≤ 0.25%), and the parameters of 45 steel (Young’s modulus To verify the accuracy of the model proposed in this paper, a test platform for normal contact stiffness was built. As shown in The roughness obtained by cutting is closely related to the equipment, tool, and cutting conditions. The machining process is very complicated, and the surface roughness varies greatly. Therefore, roughness is an important parameter for measuring machining accuracy and is the most important material uncertainty factor of machining surfaces. The national general roughness standards are Ra1.6, R3.2, Ra6.3, etc. Therefore, roughness values of Sa 1.6 μm, Sa 3.2 μm, Sa 4.5 μm, and Sa 5.8 μm, close to the national standard, were selected in this paper. The validity of the model is verified by comparative experiments. Experimental results of normal contact stiffness of mechanical bonding surfaces with different roughness could be obtained by the test bench built in Sa 1.6 μm, Sa 3.2 μm, Sa 4.5 μm, and Sa 5.8 μm. As shown in the figure, by comparing the normal contact stiffness curves under four different roughness conditions, it can be seen that the stiffness of the joint surface with low roughness is always greater than that of the joint surface with high roughness as the pressure increases, and normal contact stiffness also increases with an increase in normal contact pressure. Therefore, contact stiffness of the joint surface with low roughness is greater than that of the joint surface with high roughness. When the normal pressure is increased up to 6.3 MPa, the normal contact stiffnesses for roughness values of Sa 1.6 μm, Sa 3.2 μm, Sa 4.5 μm, and Sa 5.8 μm are 8.8 MPa/μm, 6.3 MPa/μm, 4.5 MPa/μm, and 3.5 MPa/μm, respectively. The reasons for this are analyzed from the perspective of mechanical principles. At the onset of loading, the pressure is relatively small, the deformation of the asperities is within the elastic range, the contact deformation of the joint surface is mainly elastic, and the relationship between the normal pressure and normal contact stiffness is approximately linear. However, with an increase in applied pressure, the asperities deform elastoplastically. The contact deformation of the joint surface is mainly elastoplastic, and the relationship between normal pressure and normal stiffness shows a nonlinear trend. When the normal contact pressure is high, the asperities begin to undergo plastic deformation, the contact deformation of the joint surface is mainly plastic, and even the substrate material of the joint surface begins to undergo deformation. The asperity deformation gradually enters a stage of complete plastic deformation. The relationship between normal pressure and normal contact stiffness appears nonlinear, the normal contact stiffness gradually tends towards a fixed value, and the slope of the curve is close to horizontal. From the perspective of surface-topography characteristics, the reasons are as follows: under the same pressure, the joint surface of the specimen with low roughness has a large density of asperities, a large number of contact asperities, and the relative deformation is smaller than that of the joint surface with high roughness, resulting in a relatively high contact stiffness value. Moreover, surface corrugability, basic asperity parameters, and average specimen height are also different, resulting in a large gap in contact stiffness. The above analysis shows that roughness has a great impact on the performance of mechanical parts. Improving machining accuracy and reducing roughness can improve the normal contact stiffness of parts and improve the stability of mechanical equipment.Sa 1.6 μm, Sa 3.2 μm, Sa 4.5 μm, and Sa 5.8 μm. As shown in the figure, by comparing the stiffness curves under four different roughness conditions, it can be seen that in the test with a specimen roughness of Sa 1.6 μm, when normal pressure reaches 2.98 MPa, experimental stiffness reaches 5.62 MPa/μm. The stiffness curve of this model intersects the experimental stiffness curve. When normal pressure is less than 2.98 MPa, experimental stiffness is slightly less than the numerical simulation value of this model. When normal pressure is greater than 2.98 MPa, experimental stiffness is slightly greater than the numerical simulation value of this model. When the normal pressure is 5.09 MPa, the numerical simulation value of the stiffness of this model is 7.58 MPa/μm, and the experimental stiffness is 7.78 MPa/μm. The curve has slightly deviated, and the maximum relative error is 2.56%. The roughness is Sa 3.2 μm. When normal pressure reaches 3.43 MPa, experimental stiffness reaches 4.37 MPa N/μm, and the stiffness curve of this model intersects the experimental stiffness curve. When normal pressure is less than 3.43 MPa, experimental stiffness is slightly less than the numerical simulation value of this model. When normal pressure is greater than 3.43 MPa, experimental stiffness is slightly greater than the numerical simulation value of this model. When normal pressure is 1.91 MPa, the numerical simulation stiffness of the model is 3.05 MPa/μm and the experimental stiffness is 2.96 MPa/μm. The curve has slightly deviated, and the maximum relative error is 2.92%. The roughness is Sa 4.5 μm. When normal pressure reaches 3.82 MPa, experimental stiffness reaches 3.53 MPa/μm, and the stiffness curve of this model intersects the experimental stiffness curve. When normal pressure is less than 3.82 MPa, experimental stiffness is slightly greater than the numerical simulation value of this model, and when normal pressure is greater than 3.82 MPa, experimental stiffness is slightly lower than the numerical simulation value of this model. When normal pressure is 1.91 MPa, the numerical simulation value of the stiffness of this model is 2.43 MPa/μm and the experimental stiffness is 2.51 MPa/μm. The curve has slightly deviated, and the maximum relative error is 2.89%. The roughness is Sa 5.8 μm. When normal pressure reaches 2.29 MPa, experimental stiffness reaches 2.11 MPa/μm. The stiffness curve of this model intersects the experimental stiffness curve. When normal pressure is less than 2.29 MPa, experimental stiffness is slightly greater than the numerical simulation value of this model, and when normal pressure is greater than 2.29 MPa, experimental stiffness is slightly lower than the numerical simulation value of this model. When normal pressure is 5.09 MPa, the numerical simulation value of the stiffness of this model is 3.17 MPa/μm and the experimental stiffness is 3.08 MPa/μm. The curve has slightly deviated, and the relative error is up to 2.89%.The above analysis shows that the stiffness curve value of this model is highly consistent with the experimental stiffness curve value, and the model has a certain application value. There is high agreement between the experimental stiffness values and the simulated model stiffness values under the four typical roughness conditions. Firstly, the new model in this paper assumes the asperities to be parabolic cylindrical asperities, which is more consistent with the actual contact situation. Secondly, according to the elastoplastic contact theory, the contact deformation of asperities is divided into the elastic deformation stage, elastoplastic deformation stage, and plastic deformation stage, which is closer to their real contact deformation state. Finally, the test device designed in this experiment is more reasonable and effective, and the test instrument is of high precision and has a higher reference value. The high coincidence between experimental stiffness values and simulated model stiffness values under four typical roughness conditions indicates that the model is not affected by various roughness conditions, which proves that the calculation method of the model is real and reliable.The above experimental stiffness data are the average values of stiffness obtained through ten experiments. To verify the superiority and application of the presented model, the presented model, the GW model, the KE model, the CEB model, and experimental results were compared and analyzed. The comparison results of contact stiffness under different roughness conditions are shown in Sa 1.6 μm, with an increase in normal contact pressure, the curve of this model and the experimental curve have the same trend, and the simulation value of normal contact stiffness is close to the experimental value. However, the stiffness curves of the GW model, the CEB model, and the KE model gradually deviate from the experimental stiffness curve, and the difference becomes greater and greater. As can be seen from Sa 1.6μm, the relative error of the normal contact stiffness value of the new model is between 0.303% and 2.56%, with a small difference. The relative error of the GW model is the greatest, reaching 157.9%, and the relative error remains unchanged during the whole loading process. When the pressure is 0.64 MPa, the relative error of the CEB model is 134%, and gradually decreases to 67.5% with an increase in normal contact pressure. When the pressure is 0.64 MPa, the relative error of the KE model is 90.3%, and gradually decreases to 24.2% with an increase in normal contact pressure. The relative errors of CEB and KE models gradually decrease because the two models considered elastoplastic deformation. With an increase in pressure, the asperities began to experience elastoplastic deformation, which made the two models closer to the experimental stiffness value compared with the GW model.As can be seen from Sa 3.2 μm, with an increase in normal contact pressure, the model curve and the experimental curve have the same trend, and the simulation value of the normal contact stiffness is close to the experimental value. However, the stiffness curves of the GW model, the CEB model, and the KE model gradually deviate from the experimental stiffness curve, and the difference becomes greater and greater. As can be seen from Sa 3.2 μm, the relative error of the normal contact stiffness value of the new model is between 0.46% and 2.92%, with a small difference. The relative error of the GW model is the greatest, reaching 152.4%, and the relative error varies between 123.3% and 152.4% during the whole loading process. With an increase in normal contact pressure, the relative error value of the CEB model increases from low to high, and then gradually decreases. When the pressure is 1.91 MPa, the relative error reaches the greatest value of 108.4%. With an increase in normal contact pressure, the relative error of the KE model increases from low to high, and then decreases gradually. When the pressure is 1.91 MPa, the relative error reaches the greatest value of 75.1%.Sa 4.5 μm, with an increase in normal contact pressure, the stiffness curve of this model and the experimental stiffness curve have the same trend, and the simulation value of normal contact stiffness is close to the experimental value. However, the stiffness curves of the GW model, the CEB model, and the KE model gradually deviate from the experimental stiffness curve, and the difference becomes greater and greater. As can be seen from Sa 4.5 μm, the relative error of the normal contact stiffness value of the new model is between 0 and 2.89%, with a small difference. The relative error of the GW model is the greatest, reaching 158.07%, and the relative error varies between 127.86% and 158.07% during the whole loading process. With an increase in normal contact pressure, the relative error of the CEB model gradually decreases from 68.4% to 43.78%, and that of the KE model gradually decreases from 46.13% to 17.56%.Sa 5.8 μm, with an increase in normal contact pressure, the curve of this model and the experimental curve have the same trend, and the simulation value of normal contact stiffness is close to the experimental value. However, the stiffness curves of the GW model, the CEB model, and the KE model gradually deviate from the experimental stiffness curve, and the difference becomes greater and greater. As can be seen from Sa 5.8 μm, the relative error of the normal contact stiffness value of the new model is between 1.68% and 2.89%, with a small difference. The relative error of the GW model is the greatest: the highest value is 201.57%, and it varies between 126.8% and 201.57% during the whole loading process. With an increase in normal contact pressure, the relative error of the CEB model varies between 98.47% and 110.26%, and that of the KE model varies between 56.9% and 73.18%.As shown in 2 +GX + H cylinder cross normal contact stiffness model is established. Then the pressure and normal displacement of the asperity in the elastic deformation stage, elastoplastic deformation stage, and complete plastic deformation stage were analyzed. Finally, the normal contact stiffness of the whole joint surface was obtained based on statistical theory. Therefore, the numerical simulation stiffness curve of this model is consistent with the experimental stiffness value. According to the above comparison results, the new model proposed in this paper is more accurate than the GW, the KE, and the CEB models.Through the comparison of the above models, it is found that the stiffness curve of the GW model has a high degree of deviation. The maximum error occurs because the GW model simplifies the combination of the rough surfaces to contact between a spherical asperity and the rigid plane. this is not the case for the actual asperities between the two rough surfaces.the contact process only considers the elastic deformation of the asperity and does not consider their elastic–plastic deformation. There is a single model calculation process, and the model is relatively simple. As the pressure increases, the deviation of the simulation stiffness value from the experimental stiffness value becomes greater. The error caused by ignoring plastic deformation is prominent, and the stiffness value deviates sharply from the experimental stiffness value. The KE model is a frictionless contact elastoplastic model between a deformable sphere and a rigid plate. The model considers the evolution of elastoplastic contact with an increase in pressure and reveals three different stages from completely elastic to elastoplastic and then to a completely plastic contact interface. It covers a wide range of normal contact stiffness values from the initial yield to a full plastic state in the spherical contact region. The model fully considers the influencing factors of plastic deformation, so the numerical simulation stiffness curve is smooth for the whole loading fitting process, and it rises with the trend of the experimental stiffness curve. Compared with the GW model curve, it is closer to the experimental stiffness value, and the error is relatively small. However, the KE model assumes that the asperity shape is a spherical convex body, and the contact between the two rough surfaces is equivalent to the contact between the smooth rigid plane and the equivalent rough surface, which does not accord with the actual contact of the rough surface. As a result, there is a certain error in the comparison between the simulated normal-contact stiffness curve and the experimental stiffness curve. The CEB model is an elastoplastic model for analyzing the contact of rough surfaces. The CEB model not only considers the elastic–plastic deformation characteristics of asperities, but also adds the volume conservation factor of asperities into the plastic deformation process. During the whole loading experiment, compared with the GW model curve, the stiffness value curve of the numerical simulation was smooth and increased with the experimental stiffness value curve. However, the CEB model assumed that the asperities were spherical and in contact with the rigid surface. The model topography assumption was inconsistent with the actual situation and deviated from the real contact law, which interfered with the simulation data results. It caused error in the numerical simulation stiffness value and the experimental stiffness value, so the accuracy of the model is poor. The model proposed in this paper first fits the contour parameters and topography characteristics of a single asperity by collecting the surface data of the rough body. Then, the simulation surface of the rough body is reconstructed according to the fitting data, and the parabolic Y = CXA novel analytical model of normal contact stiffness for mechanical joint surfaces was proposed in this paper. The main conclusions can be summarized as follows:A hypothetical surface with a higher degree of agreement with the actual surface is established. Based on the fitting of actual machined surface-topography data, a hypothetical surface with parabolic cylindrical asperity and Gaussian distribution is proposed. In this hypothetical surface, a parabolic column is used to simulate the shape of a single asperity surface, and the height distribution of the asperity is characterized by Gaussian distribution.A new normal contact stiffness model is established. Based on the hypothetical surface and combined with contact mechanics analysis of the rough surface, a general normal contact stiffness model for plane-cutting surfaces was established. This model recalculates the relationship between indentation depth and contact force in the elastic, elastoplastic, and completely plastic deformation regions of asperities, and finally obtains an analytical model of normal contact stiffness.Sa 1.6μm, the maximum relative errors are 2.56%, 157.9%, 134%, and 90.3%, respectively. When roughness is Sa 3.2 μm, the maximum relative errors are 2.92%, 152.4%, 108.4%, and 75.1%, respectively. When roughness is Sa 4.5 μm, the maximum relative errors are 2.89%, 158.07%, 68.4%, and 46.13%, respectively. When roughness is Sa 5.8 μm, the maximum relative errors are 2.89%, 201.57%, 110.26%, and 73.18%, respectively. The results show that the model in this paper is closer to the experimental results than other models, thus verifying the accuracy of the model in this paper. The normal contact stiffness of mechanical joint surfaces is of great significance to the research and analysis of mechanical contact characteristics. Attention should be paid to calculations for contact of engineering surfaces. This paper mainly considers the influence of normal contact stiffness on contact calculations. In fact, tangential contact stiffness, lubrication, vibration damping, dynamic characteristics, and other factors should also be considered in the study of the contact characteristics of mechanical joints. The influence of these factors will be examined in future studies.The accuracy of this model is verified by experimental method. To verify the accuracy of the proposed method, a contact stiffness test bed was built, and the model in this paper was compared with the experimental results. The comparison results show that the model in this paper is consistent with the experimental results, which verifies the rationality and correctness of the proposed method. In addition, the proposed model is compared with the GW model, the CEB model, and the KE model in terms of the fitting data of normal contact stiffness. The results show that when roughness is


Although these tissue level measures strongly corroborate the initial postulate that PIEZO1 plays an integral part in regulating tendon material properties and stiffness in humans, we found no detectable correlation between tendon stiffness and jumping performance in the tested population that comprised individuals of highly diverse physical fitness level, dexterity, and jumping ability.Prolonged periods of increased physical demands can elicit anabolic tendon adaptations that increase stiffness and mechanical resilience or conversely can lead to pathological processes that deteriorate tendon structural quality with ensuing pain and potential rupture. Although the mechanisms by which tendon mechanical loads regulate tissue adaptation are largely unknown, the ion channel PIEZO1 has been implicated in tendon mechanotransduction, with human carriers of the PIEZO1 gain-of-function variant E756del displaying improved dynamic vertical jump performance compared with noncarriers. Here, we sought to examine whether increased tendon stiffness in humans could explain this increased performance. We assessed tendon morphological and mechanical properties with ultrasound-based techniques in 77 participants of Middle- and West-African descent, and we measured their vertical jumping performance to assess potential functional consequences in the context of high tendon strain-rate loading. Carrying the E756del gene variant (NEW & NOTEWORTHY The E756del gene variant causes overactivity of the mechanosensitive membrane channel PIEZO1 and is suspected to upregulate tendon collagen cross linking. In human carriers of E756del, we found increased patellar tendon stiffness but similar tendon lengths and cross-sectional areas, directly supporting the premise that PIEZO1 regulates human tendon stiffness at the level of tissue material properties. The study was powered based on the jump performance data published by Passini et al. , indicatTo rule out the presence of lower limb tendinopathy, the Victorian Institute for Sports Assessment questionnaires for the Achilles (VISA-A) and the patellar tendon (VISA-P) were administered –32. FurtMorphological assessments were performed using ultrasound (US) brightness mode imaging  with a linear transducer (SL18-5). The Achilles tendon (AT) was examined with the subject lying prone on the examination bed with the foot hanging over the edge. The tendon cross-sectional area (CSA) was measured 2 cm proximal to the calcaneal insertion. In a subset of the study population (the last 39 subjects in the order of appearance for the study visit), we additionally measured AT length , as well as medial and lateral gastrocnemius muscle pennation angles, which were averaged before further processing. For patella tendon (PT) assessments, the subject sat upright with adjustable support underneath the knee with a knee flexion angle of ∼20°. PT CSA was measured 1 cm distal to the patella apex, and its length was defined as the distance between the patellar and tibial insertion. The morphological assessment and patellar tendon tensile property measurements described in the paragraph below were conducted on the dominant leg, which was defined as the leg; the subject would reportedly use for kicking a ball .Before the assessment, the participant completed a 5-min warm-up on a stationary bike at self-selected speed. The participant was then seated on the examination bed with the lower legs hanging over the edge. To determine the internal moment arm of the patellar tendon and thereby derive tendon force given an external torque, the trajectory of the lower limb during small flexion extension movements (±10°) at ∼90° of knee flexion was recorded using optical markers and an infrared tracking system , immediately followed by the determination of the position of the patellar tendon by means of a marker-equipped ultrasound transducer A. The axThe jump protocol and the derived parameters were intended to provide indicators of tendon mechanical behavior in various domains. Standing on a force plate , the participants performed maximal vertical countermovement jumps (CMJs) and drop jumps (DJs), respectively, both legged and on either single leg. For standardization purposes, the participants performed the test with bare feet and were instructed to place their hands on the hip throughout the entire maneuver. For the CMJ, the participants started in an upright position, squatted down to a self-selected depth, thrusted themselves up to jump as high as possible, and ended the task in a stable upright position upon landing A. The DJJump parameters were determined based on the vertical component (Fz) of the ground reaction force signal recorded by the force plates (sampling rate: 1 kHz). Jump height was computed based on the time in air and was intended to provide a proxy for the functional capacity of the tendons involved in the posterior chain. The jump height ratio, the ratio between DJ and CMJ height, represented tendon functional efficiency during high stress stretch shortening. The maximum instantaneous power during the propulsive phase of either jump type was computed to yield an estimate of the elastic recoil capabilities of the muscle-tendon complex. The ground contact time during the DJ was chosen as a proxy for the tendon high strain rate stiffness. At the end of the study visit, saliva samples were collected with a DNA collection kit . Genomic DNA was isolated according to the manufacturer’s instructions . The E756 locus was amplified with the primers described in Ma et al. , and theR2). We constrained the optimization procedure in that the factor encoding the presence or absence of the allele variant of interest was present in every iterated model. As a consequence of this approach, no effect estimates are reported (or available) for factors not included in the final models. A list of all factors included in the different outcome domains is provided in Supplemental Table S1 (https://doi.org/10.6084/m9.figshare.22440172.v1). Higher-order polynomials (with interaction effects) and alternative transformations were also evaluated but were deemed unsuitable in the current context (data not shown). Statistical significance was set at α = 0.05. The analysis was conducted in R  E756del carriers, of whom three were homozygous. Females were identically distributed between both groups, accounting for a proportion of 40% each. However, E756del carriers were older and less physically active on average than the noncarrier group. The two groups were comparable in average body height, but the E756del carrier group was 7.2 kg heavier on average .Descriptive statistics of the two study groups indicated tendon morphology to be comparable . Indeed,Achilles and patellar tendon length and CSA were associated with the subject height, and CSA was in addition associated with the subject’s body-mass index (BMI) .−1, P = 0.002) and Young’s modulus  compared with noncarriers .There was a large overall variability in PT stiffness and Young’s modulus . Nevertheless, E756del carriers exhibited significantly higher tendon stiffness .None of the assessed vertical jump performance measures indicated a significant difference between E756del carriers and noncarriers. Outcome parameters were associated with various confounders, with adjusted This study corroborates the role of PIEZO1 as a major regulator of tendon mechanical properties in humans. Carriers of the PIEZO1 Edel756 gain of function (GOF) allele displayed nearly 50% higher patellar tendon stiffness and Young’s modulus than noncarriers. In line with previous investigations, the observed elevation in tendon stiffness seems to be primarily a result of structural or compositional factors rather than tendon cross-sectional area, as no overt differences in tendon morphology were observed. Given that our study included only three homozygous carriers, we do not have sufficient data about the role of the carrier’s zygosity in this regard.Whereas PIEZO1 GOF carriers showed an increased DJ/CMJ height ratio compared with noncarriers in our previous investigation , the curNotably, however, the jump height ratio was associated with Achilles tendon length. A longer tendon may both increase the capacity for tendon energy storage and decrease the muscular work required for successful completion of the maneuver. Another potentially valuable parameter for assessing physical performance-relevant tendon phenotypes could be the maximum ground reaction force achieved during a plyometric jump. Provided the subject does not establish contact with the heel during deceleration, the magnitude of vertical ground contact force (Fz) in combination with relatively short contact times (compared with CMJ) would likely cause the DJ to be associated with rapid high-strain tendon elongation that in turn will be affected by tendon stiffness, which thus represents a pivotal parameter for explosive motions, such as sprinting . In the Our finding of a negative association of subject age with patellar tendon Young’s modulus is in line with and adds the existing body of knowledge on this topic . RegardiThere are limitations to this study that need to be considered. Logistical constraints prevented us from acquiring ground-truth measurements of PT moment arm length, such as those available with flexed-knee magnetic resonance imaging , 48. TheFinally, from a functional perspective, in addition to the present data derived on tendon stiffness, information regarding the implications of PIEZO1 GOF on the viscoelastic tendon properties would be desirable. Such properties could be probed by inspecting the hysteresis behavior of the tendon force over a tendon loading–unloading cycle. Although such in vivo analyses have been published previously , 52, 53,PIEZO1 GOF carriers display substantially elevated patellar tendon stiffness at an equal cross-sectional area compared with noncarriers. In untrained individuals, the difference in tendon stiffness does not translate to detectable differences in jumping performance. Our findings corroborate the premise that the PIEZO1 membrane channel is a significant factor in regulating structural and/or compositional homeostasis in human tendons and that the E756del PIEZO1 mutation is associated with an increased elastic modulus of the load-bearing patellar tendon.Data will be made available upon reasonable request.10.6084/m9.figshare.22440172.v1https://doi.org/10.6084/m9.figshare.22440172.v1.Supplemental Tables S1–S4: The authors received no specific financial support for the research, authorship, and/or publication of this article.No conflicts of interest, financial or otherwise, are declared by the authors.T.G., V.H., G.K., B.N., P.A., J.S., F.S.P., and J.G.S. conceived and designed research; T.G., V.H., G.K., B.N., and F.S.P. performed experiments; T.G., V.H., G.K., B.N., and F.S.P. analyzed data; T.G., V.H., G.K., P.A., J.S., F.S.P., and J.G.S. interpreted results of experiments; T.G. and V.H. prepared figures; T.G. and V.H. drafted manuscript; T.G., P.A., J.S., F.S.P., and J.G.S. edited and revised manuscript; T.G., V.H., G.K., B.N., P.A., J.S., F.S.P., and J.G.S. approved final version of manuscript.


Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats.Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disordersen bloc, flushed, and cold-stored.We performed a perineal  and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian , or penile, testis and its ducts  was removed The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery.We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2 h after transplantation.The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%. This condition is also called “dual incontinence” (DI) and remains a critical complication of pelvic floor dysfunction. The prevalence rate in the general population ranges between 5.3% and 9.4%, and in women, it increases to 20%–30% –5. PatieVascularized composite tissue allotransplantation—covering the face, members , trachea, and anorectal segment, among others—is a recent advancement in the field of transplantation. This innovation aims to improve the quality of life and individual function, rather than mere survival, defining a new trend for the treatment of many system dysfunctions –13.We hypothesize that pelvic floor transplantation covering the skin, pelvic muscular complex, urethra, bladder, ureter, genitalia (vagina or penile), anorectal segment, neurovascular pedicle, and secondary genital organs is a potential treatment for severe DI and complex perineal congenital disorders or injuries following extensive trauma. We have already observed in another study that the surgical technique for pelvic floor transplantation in cadavers is feasible . In this2.2.1Twenty-two Lewis rats weighing 250–300 g were used as donors and recipients in 11 pelvic floor transplantations. All procedures were approved by the research ethics committee of the University of São Paulo School of Medicine and the anesthesia was performed intraperitoneally using ketamine (30 mg/kg) and xylazine (10 ml/kg).2.22.2.1en bloc, containing the skin, muscular complex, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian in female  and the pudendal nerves (10.0 nylon). For the ureter anastomosis, we used a polyethylene stent with a minimum ID of 0.5 mm inserted in both (donor and recipient) ureter ends and secured with two 7/0 silk ligatures. The pelvic floor was positioned in its original position (orthotopic) or in the lower part of the abdominal incision (heterotopic) and fixed by stitches between pelvic floor ligaments, muscles, and skin, completing the operation . We sacr3.We performed a total of 11 consecutive pelvic floor transplantations in rats. Seven recipients were transplanted using the orthotopic model, whereas four were done with the heterotopic model. The reproductive organs were maintained in the graft, so the vascular pedicle included the gonadal vessels for their vascularization. Consequently, a long venous and arterial pedicle including the renal vessels was required. The donor/recipient size match is very important . Donor/r4.Our group and others have investigated anorectal transplantation as a potential solution for severe fecal incontinence. The initial results of this procedure in rats, swine, and canines are promising, showing a convenient functional recovery of this composite graft transplantation. Thus, these experiments suggest that anorectal transplantation would be a promising solution for severe fecal incontinence and permanent colostomy –24.The necessity of anatomic studies for our research in anorectal transplantation inspired us to develop pelvic floor transplantation. During pelvic floor dissection in cadavers and rats, we observed that the pelvic floor is a complex system working like a singular organ. They share the same vascular and neuronal pedicles that control the musculature, which promotes both urinary and fecal continence as well as sexual reproductive functions. Thus, we formulated the hypothesis that the entire structure could be transplanted as a composite graft.Araki et al. suggest that the anastomosis of pudendal vessels by super-microsurgery would be important for the recovery of pudendal function after anal transplantation, affecting all pelvic organs , 23. NevMany patients would benefit from this procedure, including those with complex perineal trauma and congenital pelvic deformation. We are currently designing new models to expand the indications of this composite graft, mainly for trauma. Another possible indication would be for sexual gender reassignment for patients with gender identity disorder (dysphoria). Gender reassignment surgeries have been indicated for these patients; however, these procedures create artificial organs and may cause intricate complications , 26. PelCurrently, we are designing in our laboratory new experiments to observe the long-term survival rates of rats in pelvic floor transplantation as well as the function of the graft. This is a highly complex procedure that requires high microsurgical skills and intensive peri- and postoperative care, including hemodynamic and biochemical monitoring, respiratory support, administration of antibiotics, fluid infusion, and potential blood transfusion.The possibility of the genitalia and adnexa transfer in the present procedure may increase the bioethical and metaphysical concerns of patients; nevertheless, these anxieties would be similar to those that exist in gender reassignment surgeries, which are already well accepted as a current therapeutic option for gender identity disorder , 26. FurPelvic floor transplantation may be a relevant option for severe pelvic floor dysfunction caused by extensive trauma or complex congenital disorders. This procedure is feasible in rats and opens the door for meaningful ethical, biotechnological, anatomical, and surgical debate.


Background: Orthostatic hypotension, defined as a decrease in blood pressure on standing, is associated with an increased risk of mortality and cardiovascular events in the general population. In addition, it has recently been suggested that arterial stiffness is independently associated with orthostatic hypotension, which may be due to a loss of the buffering effect of the ascending aorta and an early return of pressure waves. However, the specific mechanisms underlying this association remain unclear. Thus, we aimed to evaluate the association between orthostatic hypotension and arterial stiffness in the adult population.Methods: PubMed, Scopus, Web of Science, and Cochrane Library databases were searched from inception to 31 January 2022. The DerSimonian and Laird method was used to calculate pooled odds ratio (OR) estimates and their respective 95% confidence intervals (95% CI) for the association between orthostatic hypotension and arterial stiffness.Results: Overall, 11 studies were included, with a total of 10,611 subjects. Our results showed that increased arterial stiffness raises the risk of orthostatic hypotension , with a stronger association at central arterial stiffness  than at peripheral arterial stiffness .Conclusion: Our findings showed that increased arterial stiffness raises the risk of orthostatic hypotension by 40% among the adult population. Considering that orthostatic hypotension, which is usually a consequence of antihypertensive treatment, has been widely associated with the risk of cardiovascular events, appropriate control of arterial stiffness could be a clinical strategy to prevent cardiovascular morbidity and mortality. Orthostatic hypotension (OH) is a condition of increasing interest in scientific research. Certain neurological diseases are associated with OH; however, OH can also occur due to non-neurological causes. OH is defined by consensus as a decrease in systolic blood pressure by at least 20 mmHg or a decrease in diastolic blood pressure by at least 10 mmHg within the first 3 min of standing upright . When thThis physiological mechanism may interfere with the presence of atheromatous plaques by sustained high blood pressure levels or by the action of various toxicants acting on the endothelium, leading to sustained arterial hypertension and, thus, favoring an abnormal blood pressure response with orthostasis. Even in subjects without baseline hypertension, OH is associated with increased arterial stiffness, , as measHowever, there is limited evidence supporting an association between OH and arterial stiffness, and no meta-analysis has amalgamated this evidence or synthesized this relationship. Thus, the purpose of this systematic review and meta-analysis was to provide a synthesis of the evidence regarding the relationship between OH and arterial stiffness, as measured by its reference standard, PWv.This study, a systematic review and meta-analysis, was performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement  and was A systematic search was conducted independently by two reviewers (I.C.-R. and A.S.-L.) and was performed through four databases, namely, Scopus, PubMed, Cochrane Library, and Web of Science, from their inception to 13 March 2022. To perform the search, the following free terms combined with Boolean operators were used, following the PICO  strategy: “Adults,” “Adult population,” “Adult subjects,” “Arterial stiffness,” “Pulse wave velocity,” “PWv,” “Aortic stiffness,” and “Orthostatic hypotension” . FurtherStudies on the association between OH and arterial stiffness were included in this systematic review and meta-analysis. The inclusion criteria were as follows: i) population: adult subjects with pathologies; ii) exposure: arterial stiffness measured by PWv; iii) comparison: subjects with OH versus subjects without OH; and iv) outcome: OH defined as a decrease in SBP of at least 20 mmHg and/or DBP of at least 10 mmHg. We excluded i) review articles, editorials, or case reports; ii) studies that did not include cross-sectional data on the association between OH and arterial stiffness; and iii) articles that were not written in English or Spanish.Study selection, data extraction, and quality assessment of the studies were performed independently by two researchers (I.C.-R. and A.S.-L.), excluding those studies that did not meet the eligibility criteria. Disagreements were resolved by consensus or with the intervention of a third researcher (V.M.-V.).The quality assessment tool for observational cohort and cross-sectional studies from the United States National Institute of Health National Heart, Lung, and Blood Institute  was usedI2 statistic , moderate (30%–60%), substantial (60%–75%), or considerable (75%–100%). The corresponding p-values were also considered.The DerSimonian and Laird random-effects method  was usedtatistic , which rSensitivity analysis  was conducted to assess the robustness of the summary estimates. Subgroup analyses were performed according to mean age (<65 or >65 years). Random effects meta-regression analyses addressed whether mean age, percentage of female subjects, smoking history, hypertension, and diabetes mellitus prevalence modified the association between OR and arterial stiffness. Finally, publication bias was assessed using Egger’s regression asymmetry test  using a All statistical analyses were conducted with Stata SE software, version 15 .In total, 11 studies  were incThe overall risk of bias for studies examining the association between OH and arterial stiffness was fair in 45.5% of the studies and poor in 54.5% . For allI2 = 68.2%; p = 0.000) . The heterogeneity of this estimate was substantial (= 0.000) .2 = 24.1%; p = 0.253) , with no significant heterogeneity (I= 0.253) .2 = 64.0%; p = 0.016) , with substantial heterogeneity (I= 0.016) .The pooled OR estimate for the association between OH and arterial stiffness was not significantly modified (in magnitude or direction) when data from individual studies were removed from the analysis one at a time.p = 0.028) , and the pooled OR estimate showed significant results in subjects >65 years for increased arterial stiffness  . Random-= 0.028) .p = 0.000). Additionally, publication bias was found in central arterial stiffness (p = 0.050) (p = 0.003)   and peri= 0.003) .This is a novel systematic review and meta-analysis to evaluate the association between OH and arterial stiffness in adults. Our findings provide a synthesis of the evidence supporting the observations that increased arterial stiffness measured by PWv is associated with a 40% higher risk of OH. Additionally, our findings show that the risk of OH is higher in central arterial stiffness (cf.-PWv) than in peripheral arterial stiffness (ba-PWv), at 50% and 29%, respectively.Several studies have reported that OH is a predictor of cardiovascular disease (CVD) events  based onFurthermore, our results showed a higher risk of OH associated with central arterial stiffness than with peripheral arterial stiffness. This could be explained by structural differences between central and peripheral arteries as central arteries have a greater number of smooth muscle cells and elastin. . The patIn addition to the main findings of this systematic review and meta-analysis, the meta-regression analysis showed that, in studies with larger numbers of women, the risk of OH associated with increased arterial stiffness decreased. This suggests that the underlying mechanisms of pressure-dependent arterial stiffness differ by sex. However, evidence supporting this idea is limited , and a bSome limitations to this study that could have compromised our results should be noted. First, the assessment of OH could have varied among the included studies (between 0 and 5 min). Second, there was evidence of significant publication bias with the Egger test, and the results of unpublished studies could have modified the results of our meta-analysis. Furthermore, the association between OH and arterial stiffness has only recently been investigated, and this may have been a source of publication bias. Third, the pooled OR for PWv and ba-PWv analysis showed a substantial risk of heterogeneity; therefore, our results should be interpreted with caution. Fourth, since PWv has been the accepted gold standard for non-invasive measurement of arterial stiffness , only stIn summary, our data suggest that increased arterial stiffness, measured by PWv, increases the risk of OH and is higher for central arterial stiffness than peripheral arterial stiffness. Considering that OH, which is usually associated with antihypertensive, antiparkinsonian, and antidepressant treatments, has been widely associated with the risk of cardiovascular events, appropriate control of arterial stiffness could be a clinical strategy to prevent cardiovascular morbidity and mortality.