Infection of peripheral arterial vascular grafts and stent-grafts represents a complex surgical scenario, with a number of proposed management strategies. Surgical removal of infected material with adjunctive arterial reconstruction is often required. However, surgical removal is often difficult and complex. This case study demonstrates an infected Viabahn stent-graft between the external iliac artery and the superficial femoral artery, with arterial autolysis of the common femoral artery and proximal superficial femoral artery, in which a hybrid technique combining remote endarterectomy and surgical debridement was used to remove the infected stent-graft. Clinical experience dictates that radical excision of infected material and extra-anatomical bypass in a noninfected field is the treatment of choice.A 71-year-old woman, with a history of hypertension, dyslipidemia, hypothyroidism, and morbid obesity (body mass index 40), initially presented with one-block calf claudication and nocturnal rest pain of the right leg. Angiography demonstrated heavy calcification within the right external iliac (EIA), common femoral (CFA), and profunda arteries (PFA), and occlusion from the origin of the superficial femoral artery (SFA) to popliteal artery. A femoropopliteal in situ bypass with iliofemoral endarterectomy, extended profundoplasty, and bovine pericardial patch  arterioplasty was performed. The saphenous vein graft originated from the bovine patch. She was discharged on oral antibiotics given her high risk for wound infection.She presented 1 month later with infection and bleeding in the right inguinal incision. Angiography demonstrated a patent graft, and computed tomography suggested an infected hematoma. This was initially treated with intravenous (IV) antibiotics. However, secondary to hemorrhage from the groin, she underwent emergency excision of the infected pseudoaneurysm and bovine patch via a right flank retroperitoneal incision to control the inflow external iliac artery; she then underwent vein patch arterioplasty of the CFA and PFA, excision of the proximal portion of the previous femoropopliteal bypass due to sepsis, and reconstruction of the right femoropopliteal bypass using the left long saphenous vein. Because of extensive sepsis and debridement, a full thickness skin, fat, and muscle flap was rotated from the anterior thigh to the right groin. The patient bled postoperatively, necessitating stenting grafting of the right CFA into the right PFA using a 10 mm × 100 mm Viabahn  stent graft, which occluded her femoral-to-popliteal bypass.Staphylococcus aureus. The patient was reluctant to undergo further surgery. After negative blood cultures, a 10 mm × 150 mm Viabahn graft was deployed extending from the EIA into the previously placed graft, thereby excluding a large false aneurysm proximal to the original stent graft. She was discharged and remained on a continuous 2-year course of IV antibiotics due to a chronically draining sinus in the right groin, and positive Escherichia coli, Enterobacter cloacae, methicillin-resistant S. aureus, and Klebsiella pneumonia cultures. Despite ongoing antibiotics, eventually the Viabahn graft eroded the overlying skin and was visible in the right groin . Using a vertical incision from the lower anterior abdominal wall to the right thigh, the PFA (at the level of the second perforating muscular branch) and proximal CFA were exposed, and vascular control was obtained. The CFA and proximal PFA were autolyzed by sepsis, and only the stent-graft remained . SimultaAfter confirming occlusion of the right EIA via angiography, the distal profunda femoris was clamped and the stent graft was transected. Using sharp dissection, the distal portion of the stent graft was excised to the mid-profunda. Attention was then directed proximally. Direct moderate traction on the transected end of the stent-graft did not dislodge it. An EndoRE remote endarterectomy device (LeMaitre Vascular) was placed around the exposed graft, similar to an intimal core during remote endarterectomy  and 3. TPostoperatively, the patient had minor wound sepsis. The patient has been followed yearly for 4.5 years with duplex scanning of the patent cross-femoral venous bypass. She has had full wound healing and remains asymptomatic.,Although uncommon, peripheral extra-anatomical graft and endovascular stent-graft infection can create complex surgical scenarios with significant patient morbidity. Incidence of infected peripheral bare-metal stents is estimated at 1 in 10,000,,,,,Arterial infection can cause arterial destruction in the absence of foreign material; however, the presence of foreign material further predisposes ongoing arterial suppuration and degradation.Remote endarterectomy has been shown to be safe for the management of peripheral arterial disease, though with variable results.Given the formidable operative morbidity and mortality associated with stent infections, a hybrid surgical technique was employed in this case. Accordingly, retroperitoneal exposure was avoided, fluoroscopy-guided remote endarterectomy reduced surgical invasiveness in a high-risk patient, and removal of infected prosthetic material promoted wound healing. The treatment principles for management of infected covered stents in peripheral arteries mirror those of infected aortic endografts of the abdominal aorta—surgical explantation of the infected graft.


The creative cruxes are as followings:  Specifications tableMethod detailsThe stocky beam involved in this method is the solid-mechanics model for two kinds of structural members in contemporary engineering practice. The first type of the members is the box beams utilized in high-rise highspeed railways or in high-rise highways . The secThe common characteristics of these two types of structural members in geometry are: (1) the ratio of length to the maximum transverse dimension (width or height) is less than 5; (2) their cross sections are noncircular configurations.The cross section of the box beam is neither an open thin-walled cross section nor a closed thin-walled cross section, but a box section with variable wall thickness and wide flange, viz., a combination of a closed box (single- or multi-cell box) with variable wall thickness and two cantilever beams with a variable depth , and theThe common feature of these two types of structural members in material properties is that they are a combination of steel structure and concrete one, that is, they are composite members ,3.The common working state of these two types of structural members is that they are often staying in the stress state of constrained torsion.The torsion inducement of the box beam originates from: (1) the nonuniform distribution of vehicle loading in the width direction on the bridge deck; (2) wind loading and seismic loading.Usually, high-rise highspeed railways or high-rise highways are fundamentally built in mountainous areas, and the distance between the body of the box girder bridge and the bottom of the valley is often hundreds of meters. In this environment, the effects of transverse wind loading and seismic loading on the bridge structure must be considered. And the uncertainty in the acting direction of wind loading and seismic loading will inevitably lead to the torsion of the bridge structure.In fact, the bridge collapse accidents see  also verLike the collapse of bridge structures, the failure form of a high-rise building structure after a shear-wave earthquake is also caused by the torque acting on the whole structural system induced by the external factors beyond its own anti-torsion ability. From the site of the earthquake damage of building structures see , the mosThe above facts show that torsional failure is the most important failure form of high-rise bridge structures and high-rise building structures. However, the traditional structural analysis methods are insurmountable to analyze the mechanics behavior of above-mentioned structural members of modern bridge structures and of super high-rise building under torsion because the cross-sectional shapes and material properties of the members adopted in the structural systems are beyond the application scope of the existing beam theory. Thusly, there is a strong requirement for finding new beam theory and new analysis method for these kinds of structural members.(1)whether the member is a beam is not distinguished by its aspect ratio, but by the stress state of the member, viz., as long as the stress state of any point in the member only has no more than 3 stresses, i.e., there is only normal stress and shear stress on the cross section while there is no normal stress on the other two pairs of lengthwise sections perpendicular to the cross section of the member see , the mem(2)the axis of the beam is the locus of the minimum torsional stiffness centres (MTSC) of all cross sections, not the locus of the geometric centres of all cross sections of the beam. The formula for determining the MTSC is as follows:Stocky beam theory (3)when establishing the out-of-plane strain law of the cross-section under stress, the plane-section hypothesis utilized by the traditional beam theory is no longer employed, but the mathematical approximation method is adopted to develop the out-of-plane strain law of the cross-section of a beam after deformation. For example, the out-of-plane deformation of the beam shown in For the meaning of the symbols in the formula and the creation process of the formula, please refer to the literature x direction of the lengthwise lines parallel to the x axis , respectively.The geometric meaning of this mathematical expression is a family of curved surfaces. For a specific cross section On the premise of ignoring the in-plane deformation of the cross section, the crosswise displacements of the beam caused by various factors  are expressed as in which, x axis in the y direction and in the z direction, respectively; x axis.The meaning of the symbols in the formula is the same as that explained in literature y direction and in the z direction at any point  on the cross section of the beam caused by the coupling action of shearing, bending and torsion. The main reason for the coupling of bending and torsion is that the actual rotational centre (MTSC) of the cross section during torsion is not consistent with the ideal torsional centre . When the two centres are inconsistent, if the cross section does not rotate about the axis connected by the ideal torsional centres, the beam will produce bending deformation as well as torsional deformation; if the torque acting on the cross section does not rotate about the ideal torsional centre, the beam will produce bending deformation as well as torsion deformation (5)The concepts of neutral axis, centroid principal axes, moment of inertia of cross section about neutral axis, and etc. used in traditional beam theory and related to plane section hypothesis; and the concepts of sector area and sector pole in Vlasov beam theory will no longer exist in stocky beam theory. The stiffness characteristics related to the deformation of the cross section of a stocky beam are expressed by 4 stiffness matrices: the matrix of tension-compression stiffness, of bending stiffness, of warping stiffness and of shear-torsion coupling stiffness.After the description of the displacement mode of the stocky beam under the possible stress state, including the restrained torsion, viz., on the basis of the mathematical expressions (2) and (4), the strain field at any point in the beam can be obtained as followsBased on following three assumptions, the elastic potential energy of the beam and the work done by the load, the mathematical model of the problem can be deduced according to the energy principle in elasticity.Assumptions(a)The displacements of any one of beams after deformation are very small vis-a-vis the dimensions of that beam before deformation.(b)The in-plane rigidity of the cross section is large enough to disregard its distortion.(c)The delamination of composite beams is neglected.For example, the ordinary differential equations for the mechanics behavior of a composite box girder see  subjecteSimilarly, the ordinary differential equations and corresponding boundary conditions for the mechanics behavior of C-section special-shaped reinforced concrete columns with a 3-metres height see  under thA, B, C, D are the cross-section tension-compression stiffness matrix, anti-bending stiffness matrix, anti-warping stiffness matrix, anti-shear-torsion stiffness matrix, respectively. The form of matrix A, B, C, D is the same as that showed in the appendix of literature A, B, C and D will be presented here.Evidently, the mathematical models of the former two kinds of problems are boundary value problems of ordinary differential equations (ODE). The numerical solution of boundary value problems of ODEs is introduced in detail in reference A, B, C and D. The higher the requirement for the accuracy of the solution, the more the number of nodal lines (or nodes) employed in calculating the four stiffness matrices A, B, C and D. Generally speaking, if the stress distribution on the cross section of the beam is required, more nodes will be needed; if the overall displacement of the beam is desired, the number of nodes can be less.The solution accuracy of the mathematical model is related to the number of nodal lines (or nodes) used in calculating the four stiffness matrices A, B, C and D directly affects the solution accuracy of the mathematical model, i.e., the solution accuracy of unknown functions , the most reasonable interpolation function could be summarized.My years of research experience signifies that if the interpolation function represented by formula (2) is selected, the numerical solution of the mathematical model will be comparable to the analytical solution  employed in formula (2), while the number of nodes is related to the distribution of the material properties, to the geometric shape and to the geometric size of the cross section of the beam. In other words, the more complex the distribution of the material properties on the cross section of the beam  is defined only on the small region composed of its adjacent nodes, thusly the calculation of each element in the four stiffness matrices A, B, C and D must be completed on the small region composed of each node and its adjacent nodes, and then all the elements of the whole stiffness matrix are obtained by the global integration method.The dependence of A, B, C and D involved in the bending-torsion coupling problem induced by the action of two transverse loads and a concentrated torque at the free end of a C-shaped column shown in For instance, the calculation of 4 stiffness matrixes When compiling computer program for the calculation of the 4 matrices, the main attention should be paid on how to realize the calculation of each element of the 4 stiffness matrices, and then on how to utilize the relationship between the local code number and global code number of the small region to assemble the 4 matrices.(1)Determine the location of the minimum torsional stiffness centre (MTSC) by using formula (1).(2)x axis is the locus of all MTSCs.Establish a global coordinate system whose (3)x axis.Select nodal lines parallel to the (4)Set up a mathematical model for the problem.(5)A, B, C and D and the load vector, associated with the mathematical model.Calculate 4 stiffness matrices (6)Solve the numerical solution of unknown functions and its derivatives in the mathematical model.(7)Determinate the mechanics behavior of the stocky beam quantitatively according to the calculation results of step (6).The concrete steps for analyzing the problem of constrained torsion of stocky beams will be presented as follows.x-axis and establish a global coordinate system. Then successively take above steps (3)-(7), the mechanics behavior of the beam under the condition of pure constraint torsion will be obtained.If the mechanics behavior of the beam under the condition of pure constrain torsion is desired, the first target will become to determine the position of the torsional centre of the cross section according to the method introduced in reference Based on above mentioned methodology and analytical steps, constrained torsional problems of stocky beams with arbitrary noncircular cross-sectional shapes and with arbitrary elastic material properties can be surmounted.For example, The correctness of these computational results can be validated by the measures presented in the following section.(1)compare numerical solution with analytical oneAs delineated in section 4, the solution accuracy of the mathematical model is related to not only the number of nodal lines used in calculating the four stiffness matrices A, B, C and D, but also the calculation precision of the four stiffness matrices. Therefore, the calculation accuracy of these four stiffness matrices is very important to the final computational results of the mathematical model of the problem analyzed. In order to ensure that the calculation accuracy of the four stiffness matrices does not affect the accuracy of the final computational results of the mathematical model of the problem analyzed, the following approaches will discuss how to evaluate the calculation accuracy of the four stiffness matrices.The analytical solution mentioned here is the analytical solution of the bending problems of Bernoulli-Euler beams because they always exist For the stocky beams studied in this paper, although their aspect ratios do not meet the application conditions of Bernoulli-Euler beams, the stiffness matrices A, B, C and D, which reflect the stiffness characteristics of the cross section, are only related to the size, to the shape and to the elastic modulus of materials of the cross section, but not to the length of the beam. Therefore, in order to evaluate whether the stiffness matrices A, B, C and D can reflect the real stiffness characteristics of the cross section of a stocky beam, the length of the stocky beam can be lengthened to make it to have the length of a new Bernoulli-Euler beam, and the numerical solution of the deflection of the new Bernoulli-Euler beam under a given transverse load can be computed by the method proposed in the paper, and then the numerical solution of the deflection can be compared with its analytical one calculated by the associated formula of the new Bernoulli-Euler beam. If the two solutions are completely consistent, or very close to each other, then the computational results of stiffness matrices A, B, C and D are reasonable and effective, and then the four matrices can be employed to analyze the mechanics problems related to the stocky beam.(2)evaluate the correctness of the solution according to the objective factsWhen making the above comparison, if encountering that a stocky beam whose cross section has a nonuniform material property, a stiffness equivalence can be achieved to the beam to make it to be of a uniform material property, and then the comparison can be completed.For the constrained torsion problems of some new types of components encountered in contemporary civil engineering, there might be no way to compare the numerical results computed by using the method proposed in the paper with the numerical ones of other methods or the experimental ones because the problems themselves have gone beyond the ability scope of the existing beam theory or of the experimental approaches. In this situation, the rationality and validity of the computational results of this kind of problems can be evaluated by the objective facts that should be obeyed by this kind of problems.For example, for the constrained torsion problem of unequal-limb L-shaped concrete filled steel tubular (or steel reinforced concrete) columns, when analyzing the constrained torsion behavior of this kind of members under the action of a pure torque, the position of the torsional centre of their cross section must be determined first. However, the cross section of this kind of members is an open thick-walled section without a symmetrical axis, which is also composed of more than two kinds of materials, and the conventional method and the existing method improved on the grounds of conventional beam theory is insurmountable to determine its torsional centre position. It is also intractable to procure the position of the torsional centre of the cross section by experimental methods.In this condition, the torsional centre of the cross section of an equal-limb L-shaped concrete filled steel tubular (or steel reinforced concrete) column can be determined first. The determination of the torsional centre position of the cross section of the equal-limb L-shaped column must first utilize the computer program to calculate the four stiffness matrices A, B, C and D of the cross section, and then apply the method proposed to determine the coordinates of the torsional centre position of the cross section. If the coordinates determined are reasonable, then they must be located on the 45-degree symmetry line of the cross section, otherwise, they will be unreasonable, because an objective fact must be followed by the equal-limb L-shaped column is that the 45-degree line of its cross section is the symmetrical line of the size, of the shape and of the material properties of its cross section. The torsional centre as one of the inherent characteristics of the cross section must also be located on the 45-degree symmetry line. This is the objective fact that a reasonable calculation must not violate.When the computer program for calculating the four stiffness matrices A, B, C and D of the cross section of the equal-limb L-shaped column has passed the above evaluation, the torsional centre position of an unequal-limb L-shaped concrete filled steel tubular (or steel reinforced concrete) column can be calculated by the computer program evaluated. After the numerical solution of the coordinates of the torsional centre position of the cross section of the unequal-limb L-shaped column is procured, the rationality and validity of the numerical solution can also be evaluated macroscopically according to the size, to the shape and to the material properties of the cross section, and the numerical solution whether accord with the objective facts or not can be judged thusly.For example, the torsional centre of an unequal L-shaped concrete filled steel tubular (or steel reinforced concrete) column should approach the side of the long limb part of the cross section because the stiffness of the long limb part of the cross section is larger than that of the short limb part, being an objective fact of the inherent hallmarks of the cross section of this kind of member.The above two approaches to evaluate the correctness of the computational results have been applied in the literature (1)An innovative solid mechanics model, stocky beam, is presented in this paper. the stocky beam theory can be applied to two kinds of structural members in contemporary civil engineering structures. The first kind of structural members is the box beams adopted in the high-rise highspeed railway or highway, and the second kind of structural members is a variety of special-shaped columns adopted in contemporary tall building structures.(2)It is introduced how to use the nodal line method to express the out-of-plane warping shape of all the cross sections of a stocky beam after constrained torsion, viz., the mathematical method how to express a family of curved surfaces is developed.(3)The analysis steps for solving the constrained torsion problem of stocky beams are discussed, and the computational results about stress analysis of two torsion-bending coupling problems of two examples are also presented so as to illustrate the power of the innovative method.(4)The measures for the evaluation of the effectiveness of the innovative method proposed are presented.The problem of constrained torsion of composite members with thick-walled noncircular cross sections in contemporary civil engineering is still an unsurmountable challenge in solid mechanics. This paper presents the methodology to surmount this challenge. The main points are summarized as follows.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The appropriate distribution of temperature in the growth system is critical for obtaining a large size high quality aluminum nitride (AlN) single crystal by the physical vapor transport (PVT) method. As the crystal size increases, the influence of the crucible on the temperature distribution inside the growth chamber becomes greater. In order to optimize the field of temperature and study the specific effects of various parts of the crucible on the large size AlN single crystal growth system, this study carried out a series of numerical simulations of the temperature field of two crucibles of different materials and put forward the concept of a composite crucible, which combines different materials in the crucible parts. Four composite crucible models were established with different proportions and positions of tantalum carbide (TaC) parts and graphite parts in the crucible. Calculations reveal that different parts of the crucible have different effects on the internal temperature distribution. The axial temperature gradient at the crystal was mainly governed by the crucible wall, whereas the temperature gradient was determined by the integrated effect of the crucible lid and the crucible wall in the radial direction. One type of composite crucible was chosen to minimize the thermal stress in grown AlN crystal, which is applicable to the growth of large sized AlN crystals in the future; it can also be used to grow AlN single crystals at present as well. As a third-generation semiconductor material, AlN has the advantages of a wide band gap, high resistivity, and high thermal conductivity . Further2. After that, Liu [2, and the operational terms that allow the implementation of different models were determined. Moreover, Cai et al. [2 pressure. In the last decade, the numerical model has been constantly improved. Gao et al. [Due to the fact that the melting points of AlN are theoretically calculated to be as high as 2800 °C and the dissociation pressure to be 20 MPa, it is challenging to apply the melt Czochralski method to grow an AlN single crystal . An AlN hat, Liu  developehat, Liu  evaluatehat, Liu  for simuhat, Liu  set out i et al.  accomplii et al.  adopted i et al.  investigo et al.  designedo et al. ,18 develThe above research was all based on the small size AlN single crystal, which is below 50 mm. Since the growth process generates dislocations and defects, it is challenging to grow a larger-size AlN single crystal under the current experimental conditions. A numerical study can overcome this obstacle. The problem is solved and optimized to provide guidance and ideas for subsequent lab tests and commercial production of the AlN single crystal. The crucible is the main component used for crystal growth, and as the crystal size increases, the crucible has an increasing influence on the temperature distribution inside the cavity. Since crystals grown by the PVT method are very sensitive to temperature, and changes in temperature distribution can seriously affect the crystal growth quality, it is also necessary to study the effect of the crucible on the temperature distribution during the growth of large size AlN crystals.Based on the above, the numerical simulations are conducted to accurately restore the temperature distributions of two crucibles with different materials, graphite crucible and TaC crucible, when growing a 90 mm AlN single crystal. Furthermore, the concept of the composite crucible combining two crucible materials is proposed, and the influence of different crucible parts on the temperature distribution is obtained by changing the proportion of the two crucible materials in the crucibles. Finally, one type of composite crucible that can reduce the internal thermal stress of the AlN crystal while maintaining a regular growth rate is carried out.2 vapor, driven by the negative axial temperature gradient; the gas phase components move to the AlN seed with relatively low temperature, and adsorb, migrate, crystallize, and desorb on the growth interface. This process continues. Then, the growth interface continues to move to the AlN powder region and grows into an AlN bulk crystal. The basic process of the PVT method for growing AlN crystal can be described as follows: In a high-temperature field, AlN charge powder decomposes and sublimates to produce the gaseous components aluminum vapor (A1) and NSince the principal objective of this study deals with the optimization and simulation of the temperature field, according to , the gaspρC is the effective heat capacity, T is the Kelvin temperature, t is the time, k is the thermal conductivity, Q is the radiative heat flux, j, ɛkɛ is the emissivity, Fj,k is the view factor, and σ is the Stefan Boltzmann constant.The heat transfer governing equation is characterized as :(1)ρCp∂TThe thermal physical and material properties of the system components are shown in Since AlN crystal growth is in a nonequilibrium state, thermal stress is induced within the crystal throughout the growth process, which is the main driving force for the creation, slip, and proliferation of dislocations in the AlN crystal .rrσ, φφσ and zzσ denote the normal stresses; rzτ denotes the shear stress.Assuming that the material is a linear elastic body, the governing equations of the thermal stress field are :(3)1r∂∂rijc represents the elastic constant, rrε, φφε, zzε, rzε represent the strain components, rα, φα, zα represent the thermal expansion coefficients, and due to the hexagonal structure, the thermal expansion coefficient of AlN crystal has only two independent components, rα = φα. refT represents the reference temperature, which is chosen as the lowest temperature in the AlN seed.In addition, according to Hooke’s law of thermoelastic solids, AlN crystal is a thermoelastic anisotropic body, and the stress–strain relation of AlN crystal can be taken as :(5)εrr=Two growth systems were set up in simulation with a difference in crucible materials. According to the literature ,29, the 2. The crystal growth rate gV is deduced from the growth kinetics, which is expressed as follows [gk is the growth rate coefficient obtained from the experiment, gk = 407.539, A and B are the constants based on the thermodynamic data, A = 27.055, B = 75788, P is the internal pressure of the furnace, and ΔT and z are the difference of temperature and the length between the AlN powder and AlN seed, respectively.During the simulation of AlN crystal growth, the influence of impurities was ignored. The crucible mainly contains two vapor species, Al and N follows :(7)Vg=kgP is regarded as a fixed value in this research, P = 300 Torr. According to Equation (8), only the temperature distribution dictates the growth rate. We set the center of the crystal surface as the temperature control point. Then the growth rate of the AlN crystal was mainly related to the axial gradient of temperature in the growth region.As the gas convective is neglected in the calculation, the pressure For the purpose of increasing the diameter of the epitaxial growth crystals, it is essential to establish a reasonable temperature distribution of the as grown AlN crystal in the radial direction as well. An excessively large radial temperature gradient causes anisotropic thermoelastic stress of the crystal, resulting in the formation and propagation of various defects, such as low-angle grain boundaries (LAGB), basal plane dislocations (BPD), and so on. The multiple defects formulated during growth are the dominant limitations to AlN single crystal growth. Therefore, to successfully grow a 90 mm aluminum nitride single crystal, the thermal stress generated within it should be minimized.Current theory believes that the resolved shear stress (RSS) due to the inhomogeneous radial temperature distribution is the main driving force for creating, slipping, and proliferation of the dislocations in the grown AlN single crystal. As a reference, the Von Mises stress (VMS) can be applied to evaluate the level of the stress inside the crystal .(8)σMisWhen the VMS stress of the AlN crystal excels the critical resolved shear stress (CRSS), dislocations or even cracks occur. Therefore, reducing the VMS stress is an effective method to reduce the risk of dislocation defect formation minimizing the density of dislocations as well as the macro cracks in AlN crystal. It is assumed that the crystal surface attached to the crucible lid is rigid, while the other two surfaces of the crystal are not in contact with the crucible wall and stress-free. The boundary conditions for thermal stress calculations can be expressed as:The Von Mises stress distributions inside the grown AlN crystals in the two crucibles are shown in From the above calculations, the high thermal resistance of the TaC crucible allows for more uniform temperature distribution in the radial direction, which results in lower thermal stress.The difficulty in growing a large-sized AlN single crystal lies in the huge thermal stresses generated during the lateral growth of the crystal. As a result, the crystal defects and dislocations increase, which leads to failure growth. Judging by the calculation of this study, when a material with low thermal conductivity is used as a crucible, the crystal growth rate is high and the growth quality is high, so there is a greater potential to grow large size crystals.During the calculation, it was found that the various crucible parts had different effects on the distribution of temperature inside the crucible. Therefore, as shown in Because the longitudinal length of TaC in the composite crucible A and B occupied a very low proportion of the entire crucible, the axial temperature gradients in those two crucibles were lower. However, the gas area of the crucible is the main region for crystal growth, so variations in crucible material in this part significantly affected either the axial temperature distribution or the growth rate. Therefore, the growth rate of crucible C was the largest among the four crucibles. As for the composite crucible D, only the material of the crucible bottom is graphite, which has higher thermal conductivity, so its heat transfer effect was worse than that of C, resulting in a relatively low temperature gradient in the axial direction. As The above discussion reveals that different crucible parts seriously impact the temperature distribution within the growth chamber. The crucible wall significantly influences the axial temperature distribution, while the joint action of the crucible lid and the crucible wall affects the radial temperature distribution. Since the bottom of the crucible is far from the growth region, it has less influence on the temperature distribution within the growth region. Moreover, for the current as well as the future growth of AlN single crystal, the composite crucible formed by the crucible parts covering the crystal region with low thermal conductivity materials and the rest of the high thermal conductivity crucible part has excellent potential for the growth of larger size and higher quality AlN single crystal given the extremely low internal thermal stress in the crystal. Concerning the problem of growing an AlN single crystal with a larger size and higher quality in the future, this paper used a numerical simulation to compare the two most suitable materials for growing 90 mm AlN single crystal concerning thermophysical properties and analyzed the influence of different crucible materials on the temperature field in the AlN crystal growth cell via the PVT method. The results showed that materials with weak thermal conductivity were more suitable as crucibles for growing large size and high quality AlN crystals because of the rapid crystal growth rate as well as the lower thermal stress level of the grown crystal. Moreover, the concept of composite crucible combining graphite and TaC to examine the effect of various crucible parts on the temperature distribution of the AlN crystal growth cell was put forward. According to the result, the temperature distribution in the axial direction was strongly influenced by the crucible wall. In contrast, the temperature distribution in the radial direction was mainly influenced by the joint action of the crucible lid and the crucible wall. The composite crucible formed by the TaC part covering the crystal region and the remaining part graphite minimized the thermal stress in the AlN crystal while ensuring a high growth rate. This study also suggests that a negative radial temperature gradient is not conducive to reducing the thermal stress inside the crystal. It provides a new direction for optimizing the temperature field for growing large-size AlN single crystal in the future.


Starch is the main food source for human beings and livestock all over the world, and it is also the raw material for production of industrial alcohol and biofuel. A considerable part of the world’s annual starch production comes from crops and their seeds. With the increasing demand for starch from food and non-food industries and the growing loss of arable land due to urbanization, understanding starch biosynthesis and its regulators is essential to produce the desirable traits as well as more and better polymers via biotechnological approaches in cereal crops. Because of the complexity and flexibility of carbon allocation in the formation of endosperm starch, cereal crops require a broad range of enzymes and one matching network of regulators to control the providential functioning of these starch biosynthetic enzymes. Here, we comprehensively summarize the current knowledge about regulatory factors of starch biosynthesis in cereal crops, with an emphasis on the transcription factors that directly regulate starch biosynthesis. This review will provide new insights for the manipulation of bioengineering and starch biosynthesis to improve starch yields or qualities in our diets and in industry. As a fundamental commodity, starch was and is still widely used for human consumption in food and non-food industries ,2. SinceGBSSI, was partly mediated by tetrapyrrole intermediates, i.e., heme, in endosperm during early seed development in rice [Starch is composed of amylose and amylopectin glucan polymers, which are packaged to form the insoluble semi-crystalline starch granules . Starch  in rice , suggestThe process of starch biosynthesis in crops requires tight cooperation of various starch biosynthetic enzymes, and coordinates with other metabolisms. Until now, a great number of genes involved in starch biosynthesis have been identified in various cereals. However, despite these findings, the regulatory factors underlying starch synthesis are still poorly understood, especially regarding the regulation of starch biosynthetic genes. Therefore, the screening and identification of key regulators is vital to understanding the fundamental regulatory mechanism underlying starch synthesis. Here, we comprehensively provide an update on current knowledge on the pivotal spatiotemporal-dependent regulators of starch biosynthesis in cereal crops with a focus on transcription factors directly regulating starch biosynthesis, which will provide new insights into cereal starch yield or quality improvement on our diet as well as in industry.Starch biosynthesis is a complex process and requires various functional enzymes, which are regulated by transcription factors (TFs) and/or other regulators . TranscrTranscriptional regulation of starch biosynthesis varies with the environment, such as phytohormones and sucrose, and shows spatial-temporal gene targeting in different cereal crops. Based on the expression patterns in various tissues, genes involved in starch synthesis can be divided into two types ,20. The Oryza sativa L. [Zea mays L. [Hordeum vulgare L. [Triticum aestivum L. [bZIP factors are the first identified transcription factors to regulate starch biosynthesis ,22, and ativa L. ,24, Zea  mays L. , Hordeumlgare L. , and Tritivum L. ,27. bZIPtivum L. ,28,29, wtivum L. . Furthertivum L. , barley tivum L. , and maitivum L. , but it ADP-glucose pyrophosphorylase large subunit 3 (OsAGPL3), OsGBSSI/Wx, starch synthase IIa (OsSSIIa), BEI, OsBEIIb, and Isoamylase-type starch debranching enzyme 2 (ISA2) [BEI and GBSSI during starch synthesis [starch synthase III (SSIII) and indirectly regulate SSIIa and BEI via interaction with prolamin-box-binding factor (PBF) to mediate starch biosynthesis at transcriptional levels. Moreover, ZmbZIP91 [pAGPS1, pSSI, pSSIIIa, and pISA1).bZIPs show broad affinities with different motifs in the process of regulating starch biosynthesis. A well-studied bZIP in rice, OsbZIP58  ,29, has 2 (ISA2) ; and (ii2 (ISA2)  by bindi2 (ISA2) , whereasynthesis . Similarynthesis  could diZmbZIP91  binds toTriticum aestivum, TabZIP28 [Besides, the functions of bZIPs depend on tissue types to some extent. OsZIP58 shows highly endosperm-dependent expression during seed development ,28, but TabZIP28 , were alAGPS1, SSI, SSIIIa, and ISA1 during starch synthesis [Interestingly, ZmbZIP91  and O2  are the ynthesis , while Oynthesis  usually Oryza sativa EREBP clone 89) protein to regulate the Wx gene expression in rice [Wx promoter [In addition to the heterodimers of bZIPs  and DOF family factors , the MYC proteins also often interact with the ethylene-responsive element-binding protein (EREBP) family in their regulatory functions during starch biosynthesis. For example, one MYC-like protein, OsBP-5, has been reported to interact with the OsEBP-89 , has been reported to negatively regulate starch synthesis-associated genes both in wheat  and riceSub1C, are reported to promote starch accumulation by depressing the α-amylase gene RAmy3D in rice internodes [Multiple AP2/ERF factors usually regulate the starch synthesis genes through the induction of phytohormones, including ethylene, abscisic acid (ABA), and gibberellin GA; . Two subternodes  and leavternodes . These pternodes .ZmSSIIIa to positively mediate starch synthesis [ZmSSI promoter and indirect regulation of ZmSh2 and ZmGBSSI during seed development [GAMYB and SSI genes, respectively. However, ABI3, also named viviparous-1 (VP1), was previously characterized as one regulator of seed development in maize [Hor2 (For B-hordeins) expression in developing endosperm and activates the GAMYB-mediated Amy6.4 expression in post-germinative reserve mobilization [ZmSSI [ABA-induced AP2/ERF in starch synthesis includes at least two TFs, EREB and ABI , ATAF1/2, cup-shaped cotyledon (CUC2)) represent one of the largest families in plants and are involved in the stress-induced response during development periods ,62. Yet,Brittle 2 (BT2) and six other hypothetic genes, including Zpu1 (encoding Zea mays pullulanase-type starch debranching enzyme), GBSSI, Sh2 (for AGPase large subunit), SSV, ISA2, and SSIIa  expression and interaction with TaGAMyb, and (iii) by adjustment of the accumulation of starch by the regulation of SSIIa and Susy1.Recently, a novel NAC-type transcription factor was revealed to regulate starch biosynthesis in wheat. TaNAC019 is specifically expressed in endosperm, and functions during starch synthesis through the following ways : (i) by As the widely distributed transcription factors, MYBs are vital for a variety of biological functions. However, the functional studies of MYBs on starch biosynthesis are still scarce in cereal crops. So far, only one MYB factor has been reported as a regulator during starch biosynthesis .ZmBT1 for ZmMYB14 to function as a regulator of starch synthesis may not be through the MBSI site (TAACTG) but other sites or mechanisms, while another is that there are spatial-temporal differences between type I starch synthesis-associated genes and ZmMYB14 [Although many MYBs, i.e., ZmMYB73, ZmMYB127, ZmMYB155, and ZmMYB14, seemed to play roles in starch biosynthesis, only ZmMYB14  has been ZmMYB14 , which mRPBF was negatively regulated by SERF1, displaying contrasting expression patterns [RAmy1A was enhanced in the presence of RPBF [Hordeum vulgare. GAMYB and BPBF in the developing endosperm activates the full Hor2 expression controlled by the expression pattern of HvVP1 (VIVIPAROUS1), orthologous to ABI3 from Arabidopsis thaliana, whereas the activation of Amy6.4 in post-germinative reserve mobilization was mediated by GAMYB [DOFs show endosperm-specific expression in the regulation of starch biosynthesis . Regulatpatterns ,35, whil of RPBF ,65. One by GAMYB . So, it by GAMYB .ZmGBSSI and ZmISA1 through the combination with DOF core elements in their promoters both in vitro and in vivo [SSIIa [DOFs also mediated the synthesis of starch and seed storage proteins (SSPs) through recognition of the AAAG motif . Several in vivo , while Zo [SSIIa .GRAS transcription factors are involved in plant growth and development processes, especially for endodermis specification . BesidesOne maize TF of GRAS, ZmGRAS20, plays regulatory roles in starch biosynthesis of rice endosperm . Throughisoamylase (ISO), and thereby mediates carbohydrate anabolism [SUSIBA2 produced a rice variety with a high starch content but low methane emission [ISO1 and BEIIb, and confers tissue-specific sugar responsiveness [ISO and BE.Sugar signaling in barley2 (SUSIBA2) is a plant-specific WRKY TF that regulates gene expression in the presence of sugar, thereby mediating the communication of source-sink ,70 via aemission , suggestemission . SUSIBA2siveness ,70. Ther2-responsive CONSTANS, CONSTANS-like, and time of chlorophyll a/b-binding protein1 (CRCT).Some regulatory factors cannot be listed in any of the above groups, and thus are included independently in this section , includiFLOURY ENDOSPREM is named based on its well-recognized but viable endosperm phenotypes, which usually display a chalky and soft endosperm. So far, 16 rice floury mutants [ZmFloury3 [ mutants  and thre mutants  have bee mutants  and FLO7 mutants , as wellmFloury3  serve asmFloury3 ,75,76, tFLO2 acts as a regulatory protein that controls the biosynthesis of seed storage substances, possibly through its tetratricopeptide repeat (TPR) motifs for protein–protein interactions . At leasN-terminal transit peptide and an unknown function 1338 (DUF1338), during starch synthesis and amyloplast development [FLO7 prefers to specifically function in the endosperm periphery, and harbors two essential domains of an elopment .Floury3 (named FL3), a plant AT-rich sequence and zinc-binding (PLATZ) protein, acts as a specific regulator in maize starchy endosperm cells . FL3 plaOsCRCT displays diurnal oscillation and is mainly focused on the vegetative organs. Therefore, OsCRCT serves as a positive regulator of several starch biosynthetic genes, including AGPS1, AGPL1, Glc-6-phosphate translocator2 (GPT2), plastidial α-glucan phosphorylase1 (Pho1), and BEIIa, and contributes to starch biosynthesis in rice leaves [OsCRCT is a potential approach to improve yields for food and biofuel [The CRCT protein has been reported to be a regulator of starch biosynthesis in rice but does not seem to belong to a zinc finger motif , and cane leaves . The eff biofuel , dependiAside from the direct regulators of starch biosynthesis, many other factors also participate in the regulation of starch synthesis, partially through the post-transcriptional regulation of TFs, i.e., micro RNAs (miRNAs), or via regulators of the formation of the upstream precursors and/or downstream products of starch.miRNAs can negatively mediate gene expression at the post-transcription levels , and havSome transcription factors have been reported to mediate starch accumulation in cereal endosperms, but they participate in regulation via control of the synthesis of the downstream and/or upstream products of starch, i.e., sugar and proteins, instead of directly regulating starch synthesis. Here, we mainly concentrate on some of them , includiα- and β-zein [b-32 [pyruvate orthophosphate dikinase 1 (PPDK1) [γ-zein and 22-kDa α-zein [α-zein and 50-kDa γ-zein through the binding of the CATGT motif in their promoters.Aside from direct regulation of starch synthetic enzymes, some bZIPs are also involved in the regulation of starch synthesis via indirect ways . For exad β-zein , b-32 [2in [b-32 , and pyr (PPDK1) ,22 via ra α-zein ,87 throua α-zein  to combia α-zein , is esseO2, PBF1, ZmbZIP22, NAC130, and O11.Recently, one B3 domain-containing AP2/ERF transcriptional factor, ZmABI19 , was wel16-kDa γ-zein genes [Regulation of NAC on starch synthetic enzymes is often accompanied with a simultaneous regulation of storage protein synthesis-associated genes . Althougin genes . Howeverin genes  do not din genes . TaNAC01in genes  has beenα-zein and γ-zein [27-kDa γ-zein [γ-zein [Nkd1 (naked endosperm 1) promoter to regulate aleurone cell differentiation.Some DOF TFs have similar effects on the regulation of starch synthesis. PBF specifically binds with P-box (TGTAAAG) to mediate the synthesis of proteins , i.e., αd γ-zein . PBF cand γ-zein  to regula γ-zein . Therefoa γ-zein  during s [γ-zein , while Z [γ-zein  can bindGBSSI, in mature seeds. Another MADS TF, ZmMADS47, through the interactions with OPAQUE2, directly regulates prolamin in maize [OsGIF1 during grain filling stages [MADS-box transcription factors have attracted increasingly more attention in the studies of seed development ,90. For in maize . Interesin maize . Howeverg stages . Thus, tNKD2 and ZmDOF3 during endosperm development. Besides, it is also involved in the regulation of nutrient and carbohydrate metabolism via O2 and PBF, as well as in response to environmental stresses. Thus, OPAQUE11 may work as the focus hub in the regulatory network during seed formation [TFs of basic helix–loop–helix act as important regulators of starch synthesis during seed formation ,94. For Arabidopsis thaliana [Arabidopsis [ZHOUP1 (ZOU) is involved in the seed formation of angiosperm plants, i.e., thaliana ,96 and mthaliana . ZmZOU ithaliana . Similarthaliana  and in Abidopsis , via theStarch was and remains an essential commodity in food and non-food industries. Cereal seeds provide a great account of starch production, and thereby, starch synthesis and its regulation in seed endosperm have been investigated by researchers of breeding. The enzymes involved in starch synthesis have been well identified in cereals, but, until now, the regulatory mechanism underlying starch synthesis has not been fully understood, especially regarding the regulators on starch synthetic genes. As the key regulators mediating gene expression, the working models of transcriptional factors perform complicated networks during starch biosynthesis , and maiThe race between the increasing starch demand and the shrinking arable land has resulted in the urgency to further understand starch biosynthesis and its regulation, which is vital to produce a rational design of agronomic traits and more and better polymers with biotechnological approaches. Besides, improved cereal grain quality is also essential to consumers; however, the formation of seed quality is a highly complex process. These processes are largely adjusted with various regulators, which perform precision guidance on the cooperation of starch synthesis-related proteins and lipids. Therefore, it is insufficient for the selection of any single trait in crop breeding.Arabidopsis, only dozens of regulators, especially for TFs, have been reported in cereal crops. Thus, the traditional mutagenesis technology, combined with advanced gene editing technology , is a commonly used way to explore novel TFs, whose binding motifs can be determined with DAP-seq [Currently, the main application of cereal starch is to feed the increasing human population as a vital food source, and thus, high yields of cereals or improvement of states of starch shortage are still the key breeding targets. However, the enzymes involved in starch synthesis have been well identified in cereals, but the efforts to improve starch synthesis have failed using the simplistic one-enzyme strategy . This wa DAP-seq  and/or C DAP-seq  technoloHomo sapiens [SUSIBA2 in rice [FTO, one specific Homo sapiens gene associated with obesity and fat mass, into rice and potato largely increased the productivity and biomass [Besides, the building of regulatory networks can also help to design a rational strategy to improve starch biosynthesis. In order to achieve this, the selection and visualization of homogenized cells is key to the transcriptomic technologies  with the sapiens . The het in rice  produced biomass . Since F biomass , it is fCollectively, this review summarized the regulators underlying starch synthesis in cereal crops, and will help to provide potential applications in crop breeding and engineering efforts.


SEM and CLSM results showed that tannic acid added to the polysaccharide–starch mixture not only interacted with starch but also influenced the structure of polysaccharide gel.In this study, konjac glucomannan, κ‐carrageenan, and tannic acid were selected to study the effects of different combinations on the in vitro digestibility and physicochemical properties of wheat starch. Results showed that the addition of konjac glucomannan, κ‐carrageenan, and tannic acid could decrease the digestion of starch and increase the content of resistant starch. Besides, the two polysaccharides weakened the extent of tannic acid on starch digestion. Moreover, although the two polysaccharides had different effects on the in vitro digestion of starch, they had no significant increase in the content of resistant starch. DSC and XRD results demonstrated that the polysaccharides and tannic acid showed synergistic effects on the rebuilding of starch microstructure. FTIR results further manifested that κ‐carrageenan and konjac glucomannan could significantly increase the strength of hydrogen bonds in starch. At the same time, the addition of tannic acid would weaken the molecular interaction between polysaccharides and starch.  Two dietary polysaccharides inhibited the direct contact of tannic acid with starch. Polysaccharides and tannic acid synergistically inhibited the formation of ordered starch structure. Tannic acid weakened the molecular interaction between the two polysaccharides and wheat starch. Tannic acid was prepared into a solution of 0.01 g/ml and stored at 4℃.In the experimental groups, the addition ratio of konjac glucomannan (KGM) and κ‐carrageenan (KC) was 3%, and the addition ratio of tannic acid (TA) was 0.2%. The concentrations of KGM, KC, and TA were chosen according to the preliminary experiments and the reference  was accurately weighed, added with 30 ml distilled water, and prepared in a centrifuge tube. After mixed well with the additions, the samples were shaken in the water bath at 95℃ for 20 min. The gelatinized mixtures were prefrozen for 24 h in a −20℃ freezer and dried for 48 h in a freeze dryer  at −50℃ .G120: Glucose content in hydrolysate for 120 min (mg).TS: Total starch content (mg).2.4o), peak (Tp), and endothermic enthalpy of gelatinization (ΔH) were recorded.Differential scanning calorimetry  was used to assess the process of gelatinization. For each group, 100 mg wheat starch and 400 μl distilled water mixed well, and 10 μl of the mixture was taken out for testing. Before the thermal scanning, the sample was sealed in the gland and balanced at 4℃ for 12 h. Using an empty crucible as a reference, the prepared samples were heated from 20 to 120℃ at 10℃/min. The transition temperatures of the onset (T2.5X‐ray diffraction (XRD) patterns of the powder samples were measured with Cu‐Ka radiation using a Powder X‐ray diffractometer . The region of scanning ranged from 10º to 70º, and the speed of goniometer was 4º/min operated at 40 mA and 40 kV . Two mg powder samples were dispersed in 200 mg KBr, which then was extracted by air for 1 min using a tablet pressing machine mold. The spectra were recorded in transmission mode from 4,000 to 400 cm2.7SEM . After freeze‐drying, the samples were deposited directly on the aluminum pile with double‐sided carbon conductive tape and coated with a layer of gold. The images were obtained at 250 magnifications operated at 15 kV  under the field at 60 magnifications. The excitation wavelength was 488 nm, and the sizes of the images were 1,024/1,024 pixels. During image acquisition, each row was scanned four times and averaged to reduce noise . The significant differences (p < .05) were evaluated and displayed by different letters.Data were presented as means ± 33.1p < .05). However, the contents of SDS in each experimental group showed no striking difference, expect for group KC. In particular, due to the different ways to affect the starch digestion, group TA had the highest RS content in the experimental groups. This may be due to the interaction between tannic acid and starch . The same reduction in the inhibitory effect also occurred in the previous study , the peak temperature (TP), and the gelation enthalpy (ΔH gel) obtained from the DSC thermogram  (p <  .05). The increase in gelatinization transition temperature  reflected the more ordered crystallinity of starch. However, there was no significant difference between group TA and group control. Moreover, compared with group KC and group KGM, there was little influence on the transition temperatures in group KC + TA and group KGM + TA. This result demonstrated that tannic acid did not influence the gelatinization transition temperature . It was consistent with our previous study  reflects the energy intake of gelation, which is an indicator of the degree of molecular order loss in the particles during gelation , especially in the four groups with polysaccharides. Besides, the relative crystallinities of group KC + TA and group KGM + TA were lower than the starch with these three substances alone. This result was supported by the thermal analysis showed above. Additionally, the relative crystallinities of group KGM + TA were memorably lower than that of group KC + TA, which indicated that the inhibiting effect of KGM on starch retrogradation was better than that of KC. This discrepancy might be attributed to the interaction between the two different polysaccharide and starch.X‐ray diffractometry is applied to determine the crystalline structures of starch and its degree of crystallinity  were related to C‐O stretching, the coupling of C‐O (in the pyran ring), C‐C stretching, and C‐O‐H bending, respectively . Compared with control group, the starch granules in group KC were slightly enlarged. However, the starch granules in group KGM and group TA were reduced to different degrees, especially in group KGM. This indicated that these two polysaccharides had different effects on the starch structure. Compared with the two polysaccharides group, the group KC + TA and group KGM + TA significantly inhibited the expansion of starch molecules after the addition of tannic acid Figure . Especia4–starch) was formed. This made the starch structure more compact and further inhibited the expansion of starch, which in turn modulated the starch digestion.Our previous study showed that tannic acid reacted with starch granules and altered their physicochemical properties  and the microstructure properties, and demonstrated tannic acid reduced the starch digestion by enzyme inhibition and the changed structures . lirong zeng: Writing‐original draft (supporting). junan gong: Investigation . yalun he: Methodology . xiong liu: Data curation . ling zhang: Data curation ; Supervision . na xu: Writing‐review & editing (supporting). qiong wang: Writing‐review & editing (lead).This study does not involve any human or animal testing.


Conclusively, the current study provides a baseline data platform to secure better future therapeutic interventions against the hemorrhagic fever causing mammarenaviruses.The recent viral outbreaks and the current pandemic situation urges us to timely address any emerging viral infections by designing therapeutic strategies. Multi-omics and therapeutic data are of great interest to develop early remedial interventions. This work provides a therapeutic data platform (Mammarenavirus (MMV)-db) for pathogenic mammarenaviruses with potential catastrophic effects on human health around the world. The database integrates vaccinomics and RNA-based therapeutics data for seven human pathogenic MMVs associated with severe viral hemorrhagic fever and lethality in humans. Protein-specific cytotoxic T lymphocytes, B lymphocytes, helper T-cell and interferon-inducing epitopes were mapped using a cluster of immune-omics-based algorithms and tools for the seven human pathogenic viral species. Furthermore, the physiochemical and antigenic properties were also explored to guide protein-specific multi-epitope subunit vaccine for each species. Moreover, highly efficacious RNAs , microRNA and single guide RNA (sgRNA)) after extensive genome-based analysis with therapeutic relevance were explored. All the therapeutic RNAs were further classified and listed on the basis of predicted higher efficacy. The online platform (http://www.mmvdb.dqweilab-sjtu.com/index.phpDatabase URL:  Lassa virus (LASV), Chapare virus (CHAPV), Lujo virus (LUJV), Guanarito virus (GTOV), Junín virus (JUNV), Machupo virus (MACV) and Sabiá virus (SABV). Demographically, LASV and LUJV are considered indigenous to Africa, whereas CHAPV, GTOV, JUNV, MACV and SABV are common in American countries  (https://www.uniprot.org/) (The whole-genome sequences (L and S segments) information used in this study were retrieved from the available online platform National Center for Biotechnology Information (ih.gov/) , whereasot.org/) . Furtherot.org/) . The basin silico vaccines against each strain. To achieve the desired objectives, CTL epitopes for each protein of all species were predicted with the help of NetCTL 1.2 server (http://www.cbs.dtu.dk/services/NetCTL/) (http://crdd.osdd.net/raghava/abcpred/) server (http://tools.iedb.org/mhcii/)  epitopes, B lymphocyte (B cell) epitopes, Helper T lymphocyte (HTL) epitopes and IFN-gamma-inducing peptides. The obtained epitope sequences for each species were further utilized to design highly immunogenic and antigenic epitopes-based NetCTL/)  and furt) server . The pre/mhcii/)  that sho/mhcii/) .http://crdd.osdd.net/raghava/ifnepitope/)  . The prepitope/)  with a dpitope/)  based onhttp://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html)   for experimental processing parameters were also employed to verify the vaccine. It was performed to unveil these properties for each vaccine construct by opting for an online webserver ProtParam (https://web.expasy.org/protparam/) (https://robetta.bakerlab.org/)   was empllgpred/)  at an actparam/) . Furtherab.org/) . In thisThe genome sequences (L and S Segments) for each species were further analyzed to predict siRNAs against each virus. Herein, virus-specific VIRsiRNApred server was employed with utilizing model 2 . The modThe intricate process of database development was followed by using Apache HTTP (Hypertext Transfer Protocol) server v2.2.1.7 through open-source Linux, MySQL (My Structured Query Language) and PHP (Hypertext Preprocessor) to develop and deploy online the ‘MMV-db’ database. Front-end development and user interaction interface were designed using CSS (Cascading Style Sheets), HTML (Hypertext Markup Language), PHP, and JavaScript, which also provides searching and downloading function. For back-end development of the database WAMP  server accompanied by scripting in environments like HTML and PHP was used. Data storage, manipulation and retrieving from the databases were managed through MySQL to confer complete control over the web contents.MMV-db focus spanned from basic protein features profiling to advanced epitopes-based vaccine designs and RNA-based therapeutics for all human-infecting MM viruses. This database is a collective platform for a total of seven hemorrhagic fever-causing-related mammarenaviruses. The database includes multiple-features profiling, including genome and proteins sequences, vaccine designs and therapeutic RNAs information represented in different tabs of the developed online platform. The overall workflow of the strategy, including the data source utilized in the design of this database, has been given in The antigenic and nonantigenic proteins for each species were identified with a VaxiJen threshold scoring system . The serSimilarly, a total of 639 CTL epitopes, 2275 B-cell epitopes, 116 746 HTL epitopes and 9945 IFN epitopes were analyzed for all the mammerenavirus species. The predicted epitopes were further classified on the basis of species-specific proteomes. The total count of whole proteome-specific T-cell, B-cell, HTL and IFN-inducing epitopes were calculated for each studied species and presented as shown in The immunogenic and potential vaccine epitopes screening was performed in a sequential manner for all the seven mammarena viruses i.e. LASV, CHAPV, LUJV, GTOV, JUNV, MACV, and SABV. Moreover, the order of proteins in the results is presented as Z, L, G (representing GPC) and N (representing NP) for each species. The prediction of T-cell, B-cell and HTL epitopes obtained after protein sequence-based analysis are presented with the total number of each type of epitope for a specific protein in individual species .v1.2 was utilized (<E) were chosen as MHC binders according to the given selection criteria of the webserver. The protein-specific T-cell epitopes (First, the prediction of potential CTL epitopes related to the four L, S, G and N was performed. For this purpose, Net CTLpan utilized , and preepitopes  were furepitopes  by usingepitopes  and furtepitopes . Using tFurther evaluation made by subjecting epitope sequences to antigenicity and allergenicity prediction helped to identify putative vaccine candidates. After the extensive analysis, putative vaccine epitopes from all groups were shortlisted, with qualifying parameters for each protein of all species included in further vaccine designs.insilco and experimental cloning. Furthermore, the robetta-predicted 3D structures of final vaccine constructs for each protein of the seven mammarena species are shown in Vaccines therapy based on targeting large protein or whole organisms is considered highly effective in reducing the burden of viral infections and associated mortality  around tin vitro half-life of the vaccine constructs in mammalian reticulocytes and in vivo in yeast and Escherichiacoli were also listed. Furthermore, the aliphatic index and GRAVY value of the proposed vaccine were determined, which reflects the stability of the protein with temperature change. Similarly, the obtained negative GRAVY value indicates hydrophilic nature and improved interactions of the vaccines with nearby water molecules. The physiochemical properties of each vaccine with all the details are provided in The ProtParam server  was utilThe potential therapeutic RNAs were also identified for all the seven species of human-infecting mammarenaviruses. The genome-based analysis was performed for each species as L, S segments and whole genome. The predicted therapeutic RNAs were further characterized on the basis of efficacy scores, including siRNAs, IM/non-IM siRNAs, miRNAs and sgRNAs. The data are also presented in different tabs with the accessible necessary information in the online resource.Silencing viral genes by RNA interference is an excellent alternative therapeutic option . RegardiThe applications of miRNA interference-based therapies spans from targeting a single gene to complex cellular pathways . In our The recently advanced biological strategies also involve sgRNA-based therapeutic interventions . SignifiDespite the advancement in the field of biology, many viral disease still suffer from the lack of proper treatment i.e. vaccines or drugs. Our investigations present 28 different multi-epitopes-based protein-specific vaccine designs with a critical role in immune response induction against seven different mammarena species. Further exploration of physicochemical properties also suggests experimental feasibility of the vaccines. However, the efficacy and safety of the highly specific MEVC candidates need further demonstration through lab experiments and remain elusive. The developed online platform also offers RNA-based therapeutic options for further investigations against human-infecting MMVs. Altogether, MMV-db offers a novel predisposed source of advanced multi-epitopes-based vaccines and RNA-based therapeutics against MMV species pathogenic to humans.baab063_SuppClick here for additional data file.


Chinese Journal of Lung Cancer 1 due to disagreement between authors.We would retract our article from Challa KIRAN and Ponnala DEEPIKAAug, 2012https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969376


Before and after the intervention, participants walked shod at their preferred velocity on a fully-instrumented treadmill. Movement kinematics, kinetics and displacement of the gastrocnemius medialis muscle-tendon junction were captured synchronously using 3D motion capture and ultrasound imaging, respectively. A MANOVA test was used to examine changes in AT force, stress, strain, stiffness, Young’s modulus, hysteresis and strain energy, measured during walking, before and following strength training. All were non-significant for a main effect of time, therefore no follow-up statistical tests were conducted. Changes in joint kinematics, tendon strain, velocity, work and power and muscle activity during the stance phase were assessed with 1D statistical parametric mapping, all of which also demonstrated a lack of change in response to the intervention. This in vivo examination of tendon function in walking provides an important foundation for investigating the functional consequences of training adaptations. We found substantial increases in AT stiffness did not impact on tendon function during walking. AT stiffness measured during walking, however, was unchanged with training, which suggests that increases in stiffness may not be evident across the whole force-elongation relation, a finding which may help explain previously mixed intervention results and guide future investigations in the functional implications of tendon adaptation.Tendons are responsive to mechanical loading and their properties are often the target of intervention programs. The tendon’s mechanical properties, particularly stiffness, also govern its function, therefore changes to these properties could have substantial influence on energy-saving mechanisms during activities utilizing the stretch-shortening cycle. We investigated Achilles tendon (AT) function  Bipedal locomotion is one of the most fundamental characteristics of humans  and one In vivo estimations of Achilles tendon hysteresis range between 2%–49% in young adults, depending on the methodology . Peak strain was calculated as the largest change in length from AT length at heel strike during the stance phase only. Stiffness and Young’s modulus were also calculated from 50–100% of the AT forces experienced during walking, to identify whether the large increases in AT stiffness with training were evident during walking.Utot, J) was calculated using Utot = 0.5 (s2/E) Vt × c, where s is peak tendon stress during walking (MPa), E is Young’s modulus, Vt is tendon volume (m3) and c is a constant reflecting the ratio of stored energy returned to the system after hysteresis (i.e. c = 0.4 for 60% hysteresis). E and Vt were obtained from previously acquired data . i.e. stiffness calculated with walking may involve more of the toe-region of the force-elongation relation than with MVC. This is supported by in vitro studies which suggest the toe-region (associated with collagen uncrimping) may account for tendon strains <4% [in vivo studies that demonstrate maximum AT strain in walking is ~4% [Our findings indicate that increases in AT stiffness may not be evident across the whole force-elongation relation. Indeed, use of a force range common to both tasks may have allowed for a better initial comparison. Peak forces during walking are suggested to be 36–52% of those during MVC , 41, so ains <4% , 43 and g is ~4% .Tendon adaptation to high loads and strains is complex and may involve structural, mechanical and/or chemical changes to the tendon hierarchy. Changes that have been linked to improved mechanical properties include increased fibril size, changes in the non-collagenous matrix, increased collagen cross-linking and better fibre organization. Importantly, such modifications will affect tendon extension mechanics, which differ with strain level. At low forces, the toe-region is primarily associated with collagen un-crimping and alignment, whist at higher forces the linear region involves inter-fascicle sliding and physical deformation of the collagen structures e.g. , 46. It Tendon dimensions were unaffected by the training intervention , therefoin vivo studies do not calculate hysteresis or strain energy per se, but tendon strain patterns during functional tasks are examined, and so elastic energy storage and return can be discussed. Findings of lower tendon recoil [The results from dynamic n recoil , higher n recoil  and no cn recoil , 58—as fn recoil  found sin recoil  found ATn recoil  and shoun recoil , found iThe tendon is considered to act like a spring in bouncing gaits and impart significant energy-saving mechanisms, yet oftentimes it is deemed that energy storage and return is limited during walking. Alexander (1991) suggested that reutilization of elastic strain energy would not likely occur during walking due to its rigid inverted pendulum design. The emergence of a bipedal spring-mass model , which iTendon behaviour during functional activities has typically focussed on young, healthy individuals, but differences have been noted in populations demonstrating changes in the tendon matrix structure and composition as a result of pathological conditions or long-term adaptation. For example, diabetic patients demonstrate attenuated tendon length changes, greater stiffness and hysteresis during walking , 28, 65,in vivo tendon function during walking in relation to a training intervention designed to elicit significant tendon adaptation. It acknowledges that substantial increases in AT stiffness as a result of a training intervention, measured via MVC, may not be detectable in activities which involve different portions of the force-elongation relation. Our findings provide the foundation for examining the functional implications of tendon adaptation during higher impact activities in future research. Despite measuring a 31% increase in AT stiffness with MVC as a result of a 12-week strength training intervention, we did not identify any significant changes in tendon mechanical properties or function during walking. Importantly, substantial increases in tendon stiffness as a result of such interventions did not have a negative impact on tendon function during walking activities. This finding may be particularly relevant for clinical and ageing populations, where walking capacity is a critical contributor to quality of life, yet tendon properties can be optimised to enhance rapid force production  required for falls prevention and improved balance and stability.Whilst there now seems to be more focus on the functional implications of tendon adaptation, the relationship between tendon properties and improvements in movement economy remain unclear; it seems that there are still many outstanding questions and methodological considerations that must be overcome. To our knowledge, this study is the first to examine S1 File(XLSX)Click here for additional data file.


Humanities and Social Sciences Communications 10.1057/s41599-021-00944-1, published online 19 November 2021.Correction to: A correction has been made to the online article and PDF to ensure one of the author’s affiliations was correctly listed.International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.International Institute for Applied Systems Analysis (IIASA), Laxenburg, Austria.The original text stated that Felix Moronta-Barrios was affiliated with:International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.This has now been corrected, so that Felix Moronta-Barrios is only affiliated with: