TDDFT allowed the rationalization of both the kinetic and fluorogenic performance of the different probes. The best candidate displays a 13.8-fold turn-on measured by quantifying fluorescence intensities in live cells under one-photon excitation, whereas a value of 3 is sufficient for high contrast live-cell imaging. In addition, live-cell imaging under two-photon excitation confirmed that there was no need for washing to monitor the reaction between BCN and this probe since an 8.0-fold turn-on was measured under two-photon excitation. Finally, the high two-photon brightness of the clicked adduct (>300 GM) allows the use of a weak laser power compatible with in vivo imaging.Fluorogenic bioorthogonal reactions are promising tools for tracking small molecules or biomolecules in living organisms. Two-photon excitation, by shifting absorption towards the red, significantly increases the signal-to-noise ratio and decreases photodamage, while allowing imaging about 10 times deeper than with a confocal microscope. However, efficient two-photon excitable fluorogenic probes are currently lacking. We report here the design and synthesis of fluorogenic probes based on a two-photon excitable fluorophore and a tetrazine quenching moiety. These probes react with bicyclo[6.1.0]no-4-yn-9ylmethanol (BCN) with a good to impressive kinetic rate constant (up to 1.1 × 10 Our best fluorogenic probe enables live-cell imaging with high-contrast and no need for washing steps. However, the use of fluorescent probes is subject to several limitations, such as the intrinsic fluorescence of the tissue (autofluorescence) or a limited depth of penetration linked to the low transparency of tissues in the wavelength ranges classically used in fluorescence microscopy. Two-photon excitation fluorescence microscopy is a good alternative for overcoming these drawbacks, as it involves absorption in the near infrared (NIR) range, which minimizes the absorption and diffusion of light by biological samples. Moreover, excitation is confined to a small volume (around 1 fL) at the focal point, considerably decreasing the risk of photodamages.4 In recent decades, considerable effort has been devoted to developing two-photon excitable probes.5 In addition to photophysical criteria, fluorophores should ideally satisfy physico-chemical and biological criteria concerning solubility in water and cell permeability, for example. Probes meeting all these requirements can be conjugated to small molecules or biomolecules for labelling purposes. However, the fluorophore moiety may affect the distribution of the labelled molecule within the cell. The development of bioorthogonal reactions has been a major breakthrough, enabling the conjugation of drugs with fluorescent tags after target recognition.6 Nevertheless, distinguishing the fluorescence of the free fluorophore from that of the conjugated fluorophore can still be an issue, particularly because the reporter dye is often present in excess relative to the drug studied, to accelerate the kinetics of the bioorthogonal reaction. After incubation, it is therefore often necessary to fix the cells and wash them to remove the excess dye, which limits the usefulness of this technique for monitoring living cells. Conversely, dye washing in living cells can be time-consuming .7,8 This procedure can also result in the removal of the probe, if it is not sufficiently well bound to its target or organelle. Fluorogenic bioorthogonal probes have been developed to overcome these problems.9 The fluorescence of these probes is initially very weak or non-existent and is restored by the reaction. This so-called “turn-on” property enables unambiguous cell labelling and provides an excellent signal-to-noise ratio. The design of such probes is based on the profluorophore-quenching effect of the click handle. Azide,10–12 sydnone13–15 and tetrazine16–22 have been used to quench profluorophores via different photoinduced energy or electron transfer mechanisms. Tetrazines have been widely used, as they undergo rapid inverse electron demand Diels–Alder reactions (iEDDA) with strained dienophiles, with kinetic constants between 1 and 106 M−1 s−1.23 Tetrazine fluorogenic probes with high turn-on ratios have been developed, some of which have been used for super-resolution imaging.24–27 Impressive fluorescence enhancements, up to several thousand-fold, have been reported for some fluorogenic probes,17–19,28 but much lower turn-on ratios have been reported for red-emissive probes.29,30 Before the study by Mao et al.,30 the best turn-on ratios reported for fluorogenic red-emitting bioorthogonal probes remained at about a 50-fold fluorescence enhancement.26,29,31–35 Finally, only a few recent examples of two-photon excitable fluorogenic probes have been reported.36,37 None of these probes has both a high turn-on ratio and a high two-photon absorption capacity (reported cross-sections < 65 GM) for red-emissive probes. We decided to fill this gap by designing a series of fluorogenic probes based on an acridan scaffold. Our recently reported optimized probe, Acri-Py, meets all the criteria for use in live-cell imaging, including high two-photon brightness and red emission  —an essential feature of biocompatible fluorophores. We then envisaged different tetrazine attachments to this scaffold to compare different quenching mechanisms (versus non-conjugated Acri-et series). We also modified the distance between the fluorophore and its quencher by preparing ortho-, meta- and para-derivatives for both designs. We found that the ortho-derivatives had higher fluorogenic efficiencies than their regioisomers. The reaction rate constants of iEDDA reactions were up to 10 times higher than those reported for this type of reaction with BCN. Ortho derivatives had impressively high kinetic constants that were explained by TDDFT calculations. We then demonstrated the potential of our best fluorogenic probe, Acri-ovi, for selective protein labelling experiments and for wash-free two-photon imaging in live A549 cells.Fluorescence is a technique of choice among the various imaging methods available, due to its sensitivity and minimally invasive nature.emission .38 Finalchanisms . We chan38 The nitrogen atom of the acridan is an ideal anchor point for tetrazine attachment. We focused on the through-bond energy transfer (TBET) and photoinduced electron transfer (PeT) quenching mechanisms as we wanted to compare these designs on our two-photon excitable fluorophore. We therefore prepared two series of fluorogenic probes differing only in the link between the dye and the tetrazine. The distance between the two chromophores is known to affect PeT efficiency and should not be greater than 10 Å. TBET requires conjugation between the two chromophores. The unsaturated linker must also prevent the chromophores from being coplanar in the ground state, thereby enabling them to be electronically independent. We thus used a styryl linker , but all three regioisomers meet the distance criterion (<10 Å). The tetrazine is perpendicular to the acridine core, which is essential for TBET ethyl methanesulfonate 9 and gave good to excellent yields. We obtained the corresponding dialdehydes of the Acri-et series, by performing Williamson ether synthesis with bromomethyl tetrazine 4 as previously described.26 The final compounds, Acri-vi and Acri-et, were obtained through a Knoevenagel reaction. Conventional conditions for the Knoevenagel reaction were adapted to avoid an excess of nucleophilic base, given the sensitivity of tetrazine to nucleophiles. Indeed, mixing dialdehyde 10 and compound 6 in the presence of pyrrolidine under classical Knoevenagel conditions led to tetrazine degradation. Stoichiometric addition of pyrrolidine at 0 °C led to the formation of iminium salts without degradation. However, the addition of the N-methyl-4-methyl pyridinium salt 6 to the iminium salts releases pyrrolidine in the reaction medium. We then simultaneously added the N-methyl-4-methyl pyridinium salt 6 and various acids in order to trap the released pyrrolidine , but it is a more pertinent partner, as its iEDDA cycloadduct with tetrazine (pyridazine) is no longer able to quench fluorescence whereas the TCO-cycloadduct (dihydropyridazine) could display a residual fluorescence quenching effect.35 We then performed the click reaction between BCN and the probes and checked the purity of the products by HPLC (ESIWe then studied iEDDA adducts with (bicyclo[6.1.0]no-4-yn-9yl)methanol (BCN). BCN reacts with tetrazine more slowly than  HPLC ESI.−1 cm−1), and emission in the red window, with a maximal emission wavelength between 638 and 652 nm. All dyes are very weakly fluorescent in native forms.38 As they became fluorescent upon immobilization, their photophysical properties and those of their click adducts were determined in a buffer containing Bovine Serum Albumin (BSA) to mimic a constrained environment. We first showed that 100 equivalents of BSA were sufficient to reach the fluorescence plateau for each fluorogenic probe and its clicked product . Conversely, maximal emission wavelengths were blue-shifted between 590 and 605 nm. However, the spectra obtained were broad (from 550 nm to 750 nm), allowing detection in the far-red window. The fluorogenic probes had low fluorescence quantum yields in BSA, confirming the efficiency of fluorescence quenching. Moreover, the click adducts had fluorescence quantum yields of about 0.15, similar to that of Acri-Py, demonstrating the restoration of fluorescence upon the fluorogenic reaction  and 10 equivalents of BCN, with 100 equivalents of BSA in the buffer .ortho) ≫ turn-on (meta) > turn-on (para) for both series , both ortho derivatives reacted within 10 minutes, while the conversion of the meta and para derivatives remained incomplete after 30 minutes. Kinetic constant measurements confirmed this trend . Unexpectedly, it was much higher than that for the other probes: 18 times greater than that of its meta analog and 38 times higher than that of its para analog . This in vitro study shows that Acri-ovi is clearly the most efficient fluorogenic probe of these series, in terms of both turn-on ratio and kinetic constant.The turn-on ratios obtained were consistent with the ratios of fluorescence quantum yields, with the same ranking and similar values . Turn-onh series . This rah series . Howeveris trend . The ratovi and BCN in cell lysate was performed. A 12-fold enhancement was observed for this fluorogenic reaction, demonstrating that measurements in BSA provide a relevant in vitro model  can reflect what happens in live cells, turn-on measurement of the reaction between Acri-trans-cyclooctene (TCO), which is known to react fast and 2-methyl-N-(isopropyl)cycloprop-2-ene-1-carboxamide (CP), which, conversely, is a weak reactive partner. However, this small strained dienophile could be of interest as it can label small molecules or biomolecules without steric impact compared with large strained cycloalkynes.40,41 We selected Acri-oet and Acri-ovi as the most fluorogenic probes. We then measured their fluorescence at 2 μM in BSA-containing buffer, and their fluorescence two hours after addition of the dienophile at 20 μM . We were therefore unable to record the TP absorption spectra of these probes in buffer containing 100 equivalents of BSA as BSA is not soluble at 10−2 M in buffer. To circumvent this issue, measurements were performed in glycerol, a viscous solvent, which mimics a constrained environment (ortho) ≫ turn-on (meta) > turn-on (para) and turn-on (Acri-ovi) = 15.3 > turn-on (Acri-oet) = 9.0, Acri-ovi remaining the most fluorogenic dye (The two-photon absorption spectra of the clicked adducts were recorded by the Two-Photon Excited Fluorescence (TPEF) method. TPEF requires highly concentrated samples , the most relevant property for imaging. The brightness values obtained (up to 416 GM) were more than 20 times higher than those reported in previous studies for red-emissive compounds.36,37 Depending on the respective absorption properties of the probes and their iEDDA products with BCN, we observed that 1P turn-on can be slightly higher or slightly lower than 2P-turn-on.The two-photon excitation spectra of the probes and their clicked adducts were recorded in glycerol at room temperature in duplicate. All compounds generated similar two-photon spectra  and S7†,o, m or p) series displayed striking variations in terms of rate constants of the click reaction and fluorescence turn-on ratios. We investigated this unexpected difference in behavior between the ortho derivative and the other two derivatives, by performing a series of quantum calculations. We first analyzed the reaction path fully with slightly simplified Acri-Xvi structures in which the methyl groups of the pyridinium were replaced by protons to facilitate the search for transition states. The click reaction proceeds in two steps: inverse electronic demand Diels–Alder (iEDDA) cycloaddition followed by a retro-Diels–Alder reaction (elimination of N2) to form the pyridazine ring. The overall reaction was strongly exergonic, releasing approximately 90 kcal mol−1 . The calculated activation energy of the cycloaddition between BCN and Acri-ovi was 1.6–1.8 kcal mol−1 lower than that for Acri-mvi and Acri-pvi  method  than for Acri-mvi (1.35 meV) and Acri-pvi (0.93 meV), consistent with stronger quenching of emission by Acri-ovi. These data provide a rational basis for the greater reactivity and higher turn-on ratio of Acri-ovi.The photophysical properties of the initial Acri-Xvi and their clicked counterparts were then studied by TDDFT calculations. The theoretical and experimental absorption maxima were within the usual range for such models  method .44 The covi, to label a protein selectively in cell lysate. We first prepared and characterized human lysozyme modified with BCN by standard methods , which is considered far below that of the standard non-invasive in vivo two-photon microscopy studies.47 Thus, the combination of the low required laser power, the NIR excitation wavelength (840 nm) and the red-emitted light (600–700 nm) makes this probe a promising probe for in vivo two-photon excited microscopy.We then evaluated the potential of Acri-he probe . Howeverovi) and rate constant (k = 1100 M−1 s−1 for Acri-ovi) as TCO led to different fluorescent and nonfluorescent species. Molecular modeling provided a rational explanation for the unexpectedly much higher rate constant for Acri-ovi than for its regioisomers. The iEDDA was identified as the rate-determining step and activation energy was lower for the ortho derivative. Finally, we found that the TBET design was more efficient that the PeT design on this scaffold. We also investigated the effect of the distance between the tetrazine moiety and the fluorophore, by connecting the fluorophore in the ortho, meta and para positions. Our data indicate that the efficiency of tetrazine quenching depends on this distance, with greater quenching activity for shorter distances. This effect of the distance was already known for PeT designs, but had not been reported for TBET designs. TDDFT calculations were performed to evaluate excitonic coupling, which was found to be much greater for Acri-ovi than for Acri-mvi and Acri-pvi, consistent with the stronger quenching observed with the ortho isomer. Acri-ovi is, therefore, our optimized fluorogenic probe and suitable for use in bioorthogonal reactions, as demonstrated by its unequivocal labelling of BCN-labelled lysozyme in a cell lysate. Moreover, these probes are the best two-photon excitable fluorogenic probes obtained to date, with impressive values for both cross-section and brightness (up to 20 times higher than previously reported).37 The high turn-on measured in cells (13.8 for 1P excitation and 8.0 for 2P) allows its use without any washing steps. Live-cell imaging by two-photon microscopy showed that Acri-ovi was an efficient fluorogenic probe that could be used with a very low laser power. This work paves the way for the further development of fluorogenic probes based on the Acri-ovi scaffold including for in vivo two-photon microscopy.Two series of fluorogenic probes were synthesized in this comparative study of PeT and TBET designs on the same scaffold. The synthesis of these probes required methodological developments, in particular in order to overcome the sensitivity of tetrazine to nucleophiles. Both series of probes had interesting fluorogenic properties, with good-to-excellent reaction rate constants with BCN, a crucial criterion for bioorthogonal reactions. BCN was the best partner for fluorogenic reactions in terms of both turn-on ratio (22 for Acri-The datasets supporting this article have been uploaded as part of the ESI.†Chemical synthesis, characterization of compounds and kinetic studies were performed by M. A. and D. N.-M. Two-photon photophyiscal properties of the compounds were determined by F. B. Molecular modeling was performed by G. C. and M. A. Cellular imaging was performed by M. A. and G. F. F. M.-B. supervised the project. F. M.-B. and M. A. conceived the study and wrote the original draft. All authors commented on the manuscript and gave approval to the final version of the manuscript.There are no conflicts to declare.SC-014-D3SC01754K-s001


Social media platforms such as Twitter allow dermatologists to collaborate, share information with the public, expand their practices, and communicate directly with patients . ConcernThe content aggregator Cronycle , which hOf the top 100 accounts, 92 appeared to represent individuals and 8 were organizations . Most weAcademic citation metrics according to the h-index  and total publications  were highly variable for 81 individuals with citation profiles. Educational posts were the most common , followed by professional content 86/293, 29%), personal posts , and lastly, advertising . Top quartile accounts by Cronycle rank posted far more educational content (>50%) than other categories of posts , and the/293, 29%We offer a cross-sectional snapshot of associations between content, popularity, and academics, prompting many avenues for further work and repeat assessment. For example, it remains to be seen whether social media branding affects academic influence, or vice versa. Twitter excels at encouraging user interactions through “mentions” and “follows,” with the “hashtag” function allowing easy searching and content propagation. However, without further protections, Twitter could also risk spreading harmful misinformation as an educationally oriented platform. While Twitter verification policies are currently in flux, account registration does not require identity verification, though this could be explored in the future to highlight board-certified physician accounts, especially for international dermatologists where external credential verification resources are limited.


This study examines the numerical representation of fluid flow on the Maxwell model in a double-diffusive boundary layer over a horizontal plate. The investigation incorporates slip conditions, encompassing momentum slip, thermal slip, and suction parameters. Moreover, the study includes the inspiration of thermal radiation, heat generation, and mass transfer. The governing partial differential equations  are transformed into ordinary differential equations (ODEs) using appropriate similarity transformations. To solve these equations in conjunction with suitable boundary conditions, the bvp4c inbuilt software is implemented. This is achieved through the shooting approach employed in MATLAB. A comprehensive agreement between the numerical technique and previously published findings demonstrates its efficacy. The outcomes are presented through graphical representations and tables, showcasing various parameters such as momentum slip, temperature slip, local Nusselt number, Sherwood number, and suction parameter. The primary motivation of this research lies in investigating the behaviour of Maxwell fluid flow in the absence of slip conditions. The study of Maxwell fluid flow over a flat plate with the combined effects of suction, thermal slip, and momentum slip conditions has a wide range of practical applications that span multiple industries, contributing to improved designs, efficiency, and understanding of fluid behaviour in various systems. The main aim of this study is to present streamlined results under varying conditions, explicitly investigating the influence of suction effects and slip conditions on the flow. This study examines the numerical representation of fluid flow on the Maxwell model in a double-diffusive boundary layer over a horizontal plate. In several scientific domains, heat transfer and solute transport play an important role, including nuclear reactors, plastic extrusion, electronic appliance cooling, and polymer manufacturing. The study of suction, thermal slip, and momentum slip in the context of Maxwell fluid flow over a horizontal plate is of great importance for understanding the behaviour of complex viscoelastic fluids in practical applications. These effects influence the stress distribution, temperature profile, and velocity profile near the boundary, and their consideration is crucial for optimizing various engineering processes involving Maxwell fluid. Researchers and engineers continue to explore these effects to develop more accurate models and design guidelines for applications involving these unique fluids.et al.1 made several noteworthy discoveries in transport theory. In a numerical study, Venkatadri et al.2 discussed the MHD radiative heat transfer investigation of Carreau nanofluid flow past a perpendicular plate. Madhavi et al.3 analyzed the entropy analysis of MHD convection flow from a flat cylinder with slip. Ramesh Reddy et al.4 studied the entropy of mixed convection flows of tangent hyperbolic fluid across an isothermal wedge. Beg and Makinde5 researched the Maxwell fluid flow and mass transfer in a Darcian porous channel. Numerous researchers have explored diverse categories of non-Newtonian fluids and various geometries of Maxwell fluids. Ahmed6 described Maxwell fluid on a stretching sheet. The consequence of radiation over Maxwell fluid on a porous sheet was explored by Mukhopadhyay et al.7 Yu Bai et al. provided reports on the Maxwell nanofluid flow.8Following this, non-Newtonian fluids find applications in areas such as decreasing friction, notably in contexts such as oil pipelines. Devi et al.9 They proposed that there is a one-to-one correspondence between the temperature distribution and the profile of radiation. In the occurrence of radiation, Rashid et al.10 described a Maxwell fluid spinning over a porous three-dimensional surface. Samuel et al.11 considered energy transfer in Maxwellian radiation flow across an exothermic surface and considered the possessions of thermal conductivity & variable viscosity. Maxwell fluid flow with radiation across a surface of varying thickness was solved numerically by Elbashbeshy et al.12 Non-Newtonian Maxwell fluid flow along a linear sheet was discussed by Khan et al.13 Hayat et al.14 calculated thermophoresis and heat radiation effects using magneto-hydrodynamic Maxwell fluid on a linear sheet. Hayat et al.15 presented a non-Newtonian Maxwell fluid flow with thermal radiation's impact in a porous media-filled environment. In ref. et al. investigated a new 3D flow of a nonlinear radiative transfer equation. Numerous sectors of industry and technology can benefit from the findings of numerical research, including momentum slipping conditions and the thermal transfer mechanism. Reddy et al.17 examined the study of the magnetohydrodynamics (MHD) boundary layer slip flow of a Maxwell nanofluid across an exponentially stretching surface with convective boundary conditions. Ibrahim and Negera18 analyzed the MHD slip flow of upper-convected Maxwell nanofluid across a sheet with a chemical reaction. Gowda et al.19 examined the slip flow of Casson–Maxwell nanofluid confined over stretchable disks. Ghalib et al.20 examined the non-time-dependent MHD flow of Maxwell fluid with slip/non-slip fluid flow and Newtonian heating at the boundary. Shamshuddin et al.21 researched the bioconvection nanofluid flow. Dogonchi et al.22 analyzed the thermal and entropy investigations on buoyancy-driven nanofluid flow inside a porous enclosure with two square cylinders. Shamshuddin et al.23 showed a numerical analysis focusing on heat transfer and viscous flow within a dual-rotating extendable disk system. Pattnaik et al.24 explored the influence of varying the shape of Fe3O4-nanoparticles on energy transfer phenomena, incorporating thermal radiation in their study. In the work of Pattnaik et al.,25 a numerical simulation was carried out to observe the flow characteristics of conducting metal and metallic oxide nanofluids. Pattnaik et al.26 delved into a comprehensive study involving mixed convective-radiative dissipative magnetized micropolar nanofluid flow on a stretching surface in permeable media, considering double stratification and chemical reaction impacts. Mohanty et al.27 employed numerical methods to analyze magnetohydrodynamic (MHD) nanofluid flow on a stretching surface, taking into account radiation. Mishra et al.28 inspected the impact of radiation and cross-diffusion influence on micropolar nano-liquid flow over a stretching sheet featuring a heat source. Damseh et al.29 discussed the effects of heat generation and first-order chemical reactions in micropolar fluid flows on a uniformly stretched porous surface. Krishna et al.30 delved into the effects of Joule, Soret, and Hall impacts on MHD rotating mixed convective flow past an infinite perpendicular permeable plate. Chamkha and Khaled31 examined solutions for hydromagnetic, energy and mass transfer in the context of free convection from an inclined plate, considering internal energy generation. Rama SubbaReddy Gorla and Ali Chamkha32 investigated the free convective boundary layer flow on a non-isothermal perpendicular plate embedded in a porous medium. Kumar et al.33 studied the influence of an induced magnetic field and radiation on the magneto-convection flow of a dissipative fluid. Takhar et al.34 analysed MHD flow on a moving plate in a rotating fluid, considering the influence of a magnetic field.Radiative fluid flow is an essential part of the design of propellers, rockets, satellites, artillery, fissionable power plants, and other multifunctional reduction structures. Heat generation on a flat plate is fundamental to various engineering systems and processes. Its control and management are critical for these systems' efficient and safe operation. Engineers and researchers continually explore innovative methods to optimize heat generation and its effects, leading to technological advancements, energy efficiency, and industrial processes. The outcome of thermal radiation on a porous surface heated by convection was calculated by Hosseinzadeh 1.1Examining the flow of Maxwell fluid over a flat plate, while considering the combined influence of thermal slip and momentum slip conditions, along with the effect of suction, constitutes a research endeavour situated within the domains of fluid dynamics and heat transfer. This study has implications for industries such as polymer processing and materials manufacturing. Including slip conditions  reflects real-world scenarios where fluid-solid interactions are not purely no-slip. Studying these slip conditions is essential for applications such as microfluidics, where slip effects become significant due to the small scale of the system. The introduction of suction at the plate's surface is often used to control or manipulate the flow in various engineering applications. Understanding the impact of these boundary conditions on Maxwell fluid flow can help design systems with enhanced control over fluid behaviour.1.2According to the literature, the thermal radiation and momentum slip influence of the boundary layer over a Maxwell fluid flow on a horizontal plate in terms of heat mass transfer across a flat plate has yet to be thoroughly investigated by any other authors in the literature. All others in the literature researched only Maxwell fluid flow on a horizontal scale with the combination of fewer parameters, and few more authors have performed their work in different fluids and geometries. So, the critical goal of this study is to solve governing equations involving radiation, heat generation, velocity slip conditions, thermal slip conditions, and suction parameter. A system of ODEs was solved in MATLAB-encoded bvp4c after the similarity transformation was carried out successfully for PDEs. Validation is achieved through comparison to a current study. The results are given for streamlining the suction effect and slip conditions for different values.2u* & v* velocity mechanisms are measured along the x & y axes. Heat generation, radiation, velocity slip, and suction effect are measured. The elongation of the flat plate occurs along the x-axis. Temperature T and solute concentration C are held constant at Tw and Cw along the y-axis of the horizontal plate . The ambient concentration is denoted as C∞, respectively, at y > 0. Using the Oberbeck–Boussinesq approximation, we examine the incompressible, laminar flow of the Maxwell boundary layer across a flat plate. qr is the radiative heat flux calculated using qr = −(4σ*/3k*)∂T4/∂y. Here, σ*and k* represent the Stephan–Boltzmann coefficient and the mean absorption coefficient. Haughty that the temperature variances in the flow are small enough, T4 can be represented as a linear function of temperature. This is achieved by mounting T4 about the ambient temperature T∞ and ignoring the higher-order terms to arrive at T4 ≅ 4TT∞3 − 3T∞4 at the solution.This article developed the theory of Maxwell fluid flow in a horizontal plate's boundary layer at a steady state. The 2.1Studying Maxwell fluid flow on a horizontal plate with the combined effects of suction, radiation, thermal slip, and velocity slip conditions has applications in several fields, particularly in advanced engineering, materials processing, and aerospace.• In this scenario, studying Maxwell fluid flow with the combined impacts of suction, radiation, thermal slip, and velocity slip conditions allows engineers and researchers to optimize the extrusion process for improved film quality, reduced energy consumption, and increased production rates.• Investigating the combined effect of thermal slip and radiation to ensure that the polymer melt solidifies at the desired rate and temperature, preventing defects such as wrinkles and bubbles in the film.• Understanding how momentum and thermal slip conditions affect the velocity and temperature profiles near the flat plate can help design optimal cooling and suction systems.• Optimizing suction and radiation can lead to energy-efficient processes, reducing costs and environmental impacts.• A better understanding of the complex fluid dynamics and energy transfer in the extrusion process can improve film quality, reduce waste, and enhance product performance.2.2The continuity equation is often combined with other equations, such as the Navier–Stokes equations for fluid motion, to analyze and solve complex fluid flow problems. It provides valuable insights into the behavior of fluids and is a fundamental tool in engineering and physics (from ref. 2.3τ) to the rate of change of shear rate (du/dt) and the relaxation time (λ2) of the fluid.2.42.52.6β1) characterizes how the fluid temperature deviates from the temperature of the solid surface as one moves away from the boundary. A more considerable thermal slip length indicates a more significant departure from the solid surface temperature. In contrast, a smaller thermal slip length implies that the fluid temperature closely matches the solid surface temperature. As with the velocity slip length, the thermal slip length typically represents the distance over which the temperature gradient in the fluid influences the heat transfer behavior near the solid boundary. The suction of fluid at the boundary has a significant influence on the flow dynamics. Suction denotes the removal of fluid from the boundary. In the context of Maxwell fluids, the occurrence of suction can alter the stress distribution near the flat plate.Momentum slip occurs when there is a difference in the velocity between the fluid and the solid boundary. In Maxwell fluid flow over a horizontal plate, the momentum slip effect can modify the velocity profile near the surface, leading to changes in the boundary layer thickness and shear stress distribution. This has significant implications for drag reduction and control of fluid flow. Thermal slip refers to the difference in temperature at the fluid-solid interface, leading to heat transfer effects that affect the boundary layer development [from ref. Let us introduce dimensionless quantities to convert PDEs into ordinary differential equations (from ref.  represents injection (vw > 0) and fw > 0 represents suction (vw < 0).•  represents the Schmith number.•  represents radiation.•  represents the Prandtl number.•  represents thermal diffusivity.•  represents heat generation.• represents the magnetic field.•  represents the Eckart number.•  represents the Deborah number.• λ” and represents the relative motion between the fluid and the solid surface. Various factors, including the nature of the surface, surface roughness, and the presence of a thin layer of gas or other materials near the surface can cause the slip velocity.• Velocity slip is a phenomenon that occurs when a fluid flows on a solid surface, such as a flat plate, and the fluid velocity at the surface is different from the velocity of the solid surface itself. This effect contrasts with the “no-slip” boundary conditions, which assume that the fluid velocity at the solid surface is zero and the fluid adheres to the surface. In the case of a horizontal plate, if there is a velocity slip effect, the fluid particles near the solid surface do not adhere to the surface and have a non-zero velocity component tangential to the surface. This slip velocity is typically denoted as “β” and represents the difference in temperature between the fluid and the solid surface at the point of contact. The thermal slip effect can be caused by various factors, including the solid surface's thermal properties, a thin insulating layer, and the nature of the fluid-solid interaction.• Thermal slip, similar to velocity slip, is a phenomenon that occurs when a fluid flows on a solid surface, such as a flat plate, and the temperature of the fluid at the surface differs from the temperature of the solid surface itself. This effect is in contrast to the “no-slip” thermal boundary conditions, which assume that the fluid temperature at the solid surface is equal to the temperature of the surface. In the case of a flat plate with a thermal slip effect, it means that the fluid near the solid surface does not instantly adjust to the temperature of the solid, and there is a temperature difference between the fluid and the solid. This thermal slip is typically denoted as “PDEs often involve numerous physical parameters, such as viscosity, density, velocity, and length scales. Non-depersonalization helps simplify these equations by expressing these parameters in terms of dimensionless numbers. This decreases the number of parameters and makes the equations more manageable. Using dimensionless quantities and similarity variables, the PDEs turned into ODEs. ODEs are generally easier to solve numerically than PDEs. Non-dimensional PDEs can simplify the numerical solution process, reducing the computational effort and resources required for simulations. The use of non-dimensional quantities in converting PDEs to ODEs is a valuable technique for simplifying complex problems, making them more tractable, and providing valuable insights into the behaviour of physical systems.2.7Maxwell fluids find applications in various fields, including rheology, polymer science, and modeling certain types of complex fluids, such as certain suspensions and emulsions. Understanding the behavior of Maxwell fluids is essential for designing and analyzing systems involving these materials.2.82.92.10The Nusselt and Sherwood numbers are crucial in analyzing and designing systems involving heat transfer and mass transfer, respectively. They provide insights into the efficiency of these processes and are used to develop practical engineering solutions in various industries, including aerospace, chemical engineering, thermal management, and environmental engineering.x & Shx quantities are defined below.By engaging the Fourier and Fick's laws, Cf, Nu3This section of the report presents the numerical solution addressing the research problem. Due to the pronounced nonlinearity inherent in the problem, our numerical approach revolves around solving a set of interconnected ODEs that come with intricate boundary conditions. Dealing with these highly nonlinear boundary values represents a substantial analytical challenge that should not be underestimated. To overcome this hurdle and solve boundary value problems (BVPs) entailing multiple boundary conditions for ordinary differential equations, we employ BVP4C, a specialized solver meticulously designed for this precise purpose. The choice between these methods depends on the nature of the differential equation problem, whether it involves boundary or initial value problems. BVP4C is a numerical method used to solve boundary value problems associated with ODEs. It is particularly useful when analytical solutions are not readily available or when dealing with complex systems in science and engineering. Researchers and engineers often use software packages such as MATLAB to implement BVP4C and obtain numerical solutions to their BVPs.The substitutions are as follows:3.1Step 1: Define the boundary value problem: define the problem by defining the differential equation(s), boundary conditions, and additional parameters.Step 2: Initialize guess for solution: start with an initial guess for the solution to the boundary value problem.Step 3: Numerical integration loop: this loop iteratively refines the solution until it converges to the desired accuracy.Step 4:(a) Solve the ODE: use a numerical method such as bvp4c in MATLAB to solve the ordinary differential equations associated with the BVP.(b) Check convergence: check whether the solution has converged to the desired accuracy. If yes, exit the loop. If not, proceed to the next step.(c) If not converged, update guess: adjust the initial guess for the solution based on the current solution and repeat the integration loop.Step 5: Output solution: once the solution has converged, output the final solution to the boundary value problem.3.2et al.44 After confirming our numerical method's validity, we will present the computational results for the Maxwell model applied to a flat plate.4Q = 0.1, λ = 0.5, fw = 1.0, β = 0.5, and Sc = 2.0.This study examines the numerical representation of fluid on the Maxwell model in a double-diffusive boundary layer on a horizontal plate. The investigation incorporates slip conditions, encompassing momentum slip, thermal slip, and suction parameters. Moreover, the study incorporates the effects of radiation, heat generation, and mass transfer. By utilizing appropriate similarity transformations, the governing PDEs  are transformed into ODEs. To solve this system of equations in conjunction with suitable boundary conditions, we used built-in “bvp4c” software in MATLAB. A comprehensive agreement between the numerical technique and previously published findings demonstrates its efficacy. The outcomes are presented through graphical representations and tables, showcasing parameters such as momentum slip, temperature slip, local Nusselt number, Sherwood number, and suction parameter. Maxwell fluid flow across a horizontal plate is a popular topic of computational research in the scientific literature. Here, we have discussed the theoretical aspects of this issue, including thermal slip, momentum slip, suction, thermal radiation, Eckart number (Ec), and heat generation. Unless otherwise stated, this study's default/unchanged parameters are Pr = 6.8, Ec = 0.1, De = 0.1, Rd = 1, x is boosted with Rd, Q, and Ec while it is reduced when the values of λ, β, and fw increase. The Nusselt number Nux is a dimensionless number that plays a crucial role in flat plate boundary value problems, particularly in the context of forced convection heat transfer. The Nusselt number quantifies the convective heat transfer rate from a horizontal plate to a moving fluid. It is used to characterize heat transfer efficiency and is often employed in the analysis and design of heat exchangers, cooling systems, and various other engineering applications.x is shown in λ, fw and Sc. The Sherwood number is dimensionless and provides information about the mass transfer behavior near the flat plate's surface. It depends on factors such as the flow velocity, fluid properties, and the concentration difference between the fluid and the plate surface.ShEngineers and scientists use correlations or experimental data to determine the local mass transfer coefficient and calculate the Sherwood number for specific flow conditions. The Sherwood number is critical for predicting the mass transfer rate and concentration distribution in forced convection mass transfer situations involving flat plates. It is applicable in various fields, including chemical engineering, environmental engineering, and food processing, where mass transfer processes play a vital role.4.1β, λ, fw, and Sc. 4.2• Observing the behavior of temperature profiles, it becomes evident that as the thermal slip conditions increase incrementally, there is a noticeable reduction in temperature. Thermal slip, in this context, means the heat exchange between the fluid and the thermal flow at the wall boundary, resulting in heat loss. • In the conventional no-slip scenario, fluid particles near the wall have zero velocity, and heat transfer primarily occurs through conduction. Nevertheless, thermal slip introduces relative motion, which can impede this conduction. Conversely, the slip conditions can enhance convective heat transfer within the thermal boundary layer. The relative motion between the fluid and the solid surface promotes increased heat transport through convection. As the slip conditions strengthen, this convective heat transfer may surpass thermal conduction. Consequently, these mechanisms contribute to deviations in the temperature outline within the thermal boundary layer compared to the expected profile under no-slip conditions. The precise temperature distribution relies on the specific slip conditions, fluid properties, and flow parameters at play.fw = 0, 0.5, 1.0, 1.5) influence on the temperature outline is presented in fw leads to a fall-off in the temperature outline. Suction can also induce mixing of fluids at different temperatures, which can lead to complex temperature profiles and gradients near the boundary. The temperature profile on a horizontal plate is closely related to the thickness of the thermal boundary layer. The thermal boundary layer is the region of the fluid where the temperature changes significantly as it adjusts from the wall temperature  to the bulk temperature of the fluid. The thinner velocity boundary layer with suction also implies a thinner thermal boundary layer. Suction reduces the thickness of the thermal boundary layer, which means less fluid is available to conduct heat from the solid surface. This can result in a decrease in thermal conduction through the fluid near the plate. Despite the reduced thermal conduction, suction can enhance convective heat transfer. The thinner boundary layer and higher fluid velocity can lead to more efficient convective heat transport. This effect can dominate over the reduction in thermal conduction, mainly when the suction is strong. The combined effect of reduced thermal conduction and enhanced convective energy transfer leads to changes in the overall temperature gradient near the flat plate.• The suction parameter  influence on the concentration field is presented in fw leads to an increase in the concentration field and fall-off in the solute field. Suction refers to removing fluid at the solid boundary, and it can have several effects on the concentration distribution, such as enhanced mass removal: as the suction effect increases, more fluid or solute is removed from the vicinity of the solid boundary. This means that the concentration of the solute near the boundary reduces more rapidly. The enhanced mass removal leads to a steeper concentration gradient near the solid surface. Thinner boundary layer: the suction effect can thin the boundary layer, which is the region near the solid boundary where concentration gradients are significant. As more fluid is removed, the boundary layer becomes thinner, and the concentration within this region decreases more rapidly. Increased mass transport: with increasing suction, mass transport  from the bulk fluid to the boundary occurs at a higher rate. This results in more efficient solute removal from the solid surface's vicinity. Reduced concentration levels and higher suction levels can lead to reduced maximum concentration levels near the boundary. This is because the suction effect continuously removes solute from the fluid adjacent to the solid surface, preventing the accumulation of high concentrations. Concentration boundary conditions: depending on the specific problem and boundary conditions, the increased suction effect may alter the concentration boundary conditions at the solid surface. For example, in cases where the boundary conditions are specified as a constant concentration or as a function of time, the suction effect can influence the rate at which these conditions are approached.• The suction parameter (by considering 4.4via the Schmidt number (Sc). Thermal slip conditions arise when a temperature difference exists between the fluid and the solid surface at the boundary. Thermal slip can modify the temperature gradient in the vicinity of the solid surface. As the thermal slip parameter increases, the temperature difference between the fluid and the solid surface becomes more pronounced. The Schmidt number (Sc) establishes a relationship between momentum diffusivity (kinematic viscosity) and mass diffusivity (the diffusivity of the solute in the fluid), playing a pivotal role in mass transfer. Temperature changes, induced by thermal slip, can have implications for Sc. The interplay between heat and mass transfer is regulated by Sc. Variations in Sc, driven by thermal slip, influence the concentration profile and, consequently, the Sherwood number. Sc is a dimensionless parameter that characterizes the relative significance of momentum transfer (viscous effects) and mass transfer (diffusion effects) within a fluid. Higher Sc values imply slower mass transfer compared to momentum transfer, and they typically lead to reduced Sherwood numbers since they indicate less effective mass transfer.Consequently, this elevation in the concentration gradient results in a higher Sherwood number, indicating more efficient mass transfer. Suction also exerts an influence on heat transfer. The modified velocity profile and concentration gradient influence the thermal boundary layer, leading to alterations in the temperature distribution near the solid surface. This, in turn, affects the Sherwood number 4.5Incorporating Maxwell fluids into the study allows for more realistic modeling of complex fluids that exhibit both viscous and elastic behavior. These fluids are encountered in various practical applications, including polymer processing, biological flows, and certain types of lubricants. This research can provide valuable insights into the interplay between viscoelasticity (represented by the Maxwell fluid model) and slip effects on the fluid flow and heat transfer characteristics. Understanding how these factors interact can lead to improved designs and control strategies in applications involving such fluids. The study of Maxwell fluid flow with slip conditions and suction is inherently interdisciplinary, applying principles from fluid mechanics, rheology, heat transfer, and materials science. It can bridge gaps between these fields and promote collaboration. This research has applications in microfluidics and nanofluidics, where slip conditions become more prominent due to the small length scales involved. Understanding the behavior of complex fluids in these contexts is crucial for the design of microfluidic devices. Combining Maxwell fluids with slip and suction conditions can lead to the discovery of novel phenomena or unexpected behavior in fluid dynamics and heat transfer, which may have practical implications or stimulate further research.4.6The combined study of Maxwell fluid flow with velocity slip, thermal slip, and suction effects is theoretically and computationally complex. The mathematical equations governing such systems can be challenging to solve analytically, and numerical simulations may require significant computational resources. Analytical solutions for such complex systems may often need to be more readily available, and researchers may rely heavily on numerical methods. This can make obtaining closed-form expressions for key flow and energy transfer parameters difficult. The behavior of Maxwell fluids and the effects of slip and suction can be highly sensitive to parameters such as relaxation time, slip lengths, and suction rate. Determining the most influential parameters and their values can be non-trivial. Conducting experiments to validate theoretical and numerical findings in such complex systems can be challenging and expensive, especially at the microscale or nanoscale. Results obtained for specific combinations of parameters and boundary conditions may not generalize easily to other systems, making it necessary to carefully define relevant parameter regimes.5This study examines the numerical representation of fluid flow following the Maxwell model in a double-diffusive boundary layer on a horizontal plate. The investigation incorporates slip conditions, encompassing momentum slip, thermal slip, and suction parameters. Moreover, the study incorporates the effects of radiation, energy generation, and mass transfer. The governing PDEs  are transformed into ODEs by utilising appropriate similarity transformations. To solve this system of equations in conjunction with suitable boundary conditions, we employ the built-in “bvp4c” software in MATLAB. A comprehensive agreement between the numerical technique and previously published findings demonstrates its efficacy. The outcomes are presented through graphical representations and tables, showcasing various parameters such as momentum slip, temperature slip, local Nusselt number, Sherwood number, and suction parameter. This investigation allows us to draw the following conclusions:• A streamline profile is provided for three different scenarios: one with a no-slip effect, another with a slip effect, and the third depicting a zero-velocity profile.• The temperature profile diminishes as the thermal slip and suction effects increase.• The concentration profile decreases as the velocity slip, Schmidt number, and suction effect increase.• The Sherwood number profile increases with growing values of the suction effect in contrast to the Schmidt number and thermal slip conditions.CfSkin friction coefficientRdRadiation parameterσ*Stefan–Boltzmann constantCConcentration of the fluidvwDimensional suction effectu* and v*Velocity of the fluidCpSpecific heatDeDeborah numberkThermal conductivityfDimensionless stream functionθNon-dimensional temperatureσFluid's electrical conductivityfwDimensionless suction parameterρcp)(Heat capacityEcEckart numberμDynamic viscosityηSimilarity variableρThe fluid densityxNuNusselt numberQ1Heat generationxStreamwise coordinateqrRadiative heat fluxPrPrandtl numberC∞Concentration on the free streamβ1Dimensional thermal slip conditionTTemperature of the fluidλ1Dimensional velocity slip conditionνKinematic viscosityT∞Free stream temperatureϕDimensionless concentrationTwTemperature on the plateDBMass diffusionyCoordinate normal to the plateλ2Relaxation timeCwConcentration on the plateU∞Free stream velocityScSchmith numberλDimensionless velocity slip conditionβDimensionless temperature slip conditionfwDimensionless suction effectxShSherwood numberReReynold numberThere are no conflicts to declare.


P < 0.05; age range 45–65 y, n = 352). The binomial logistic regression controlled for sex, age, education, cardiometabolic disease risk indicators, and obesity. Previous studies using cultured cells from the brains of human donors suggest high expression in astrocytes. In snRNA-seq data from the middle temporal gyrus (MTG) of human donors, adropin expression is higher in astrocytes relative to other cell types. Adropin expression in all cell-types declines with advance age, but is not affected by dementia status. In cultured human astrocytes, adropin expression also declines with donor age. Additional analysis indicated positive correlations between adropin and transcriptomic signatures of energy metabolism and protein synthesis that are adversely affected by donor age. Adropin expression is also suppressed by pro-inflammatory factors. Collectively, these data indicate low circulating adropin levels are a potential early risk indicator of cognitive impairment. Declining adropin expression in the brain is a plausible link between aging, neuroinflammation, and risk of cognitive decline.We recently reported accelerated cognitive decline in Europeans aged > 70 years with low circulating adropin levels. Adropin is a small, secreted peptide that is highly expressed in the human nervous system. Expression profiling indicate relationships between adropin expression in the human brain and pathways that affect dementia risk. Moreover, increased adropin expression or treatment using synthetic adropin improves cognition in mouse models of aging. Here we report that low circulating adropin concentrations associate with poor cognition (worst quintile for a composite score derived from the MMSE and semantic fluency test) in late-middle aged community-dwelling African Americans (OR = 0.775,  Several types of dementia have been identified4. The most common form is Alzheimer’s disease (AD), which accounts for 60–80% of cases and is defined by the spread of extracellular amyloid-β plaques, intracellular tau tangles, and neuronal death5. Risk for dementia increases with advanced age; about 1-in-3 people aged 80 years of older develop dementia3. Mild-cognitive impairment (MCI) is often the first sign of dementia, with one-third of people with MCI developing AD within 5 years3. In the absence of widely available effective therapies that prevent or delay the progression of dementia, the prevalence of this dementia is predicted to increase as gains in life expectancy result in aging of the population.Dementia is a blanket term used to describe the progressive, irreversible loss of intellectual abilities that result from neurodegenerative diseases8. Some of the blood-based biomarkers reflect the accumulation of amyloid and neurofibrillary tangles in the brain8. Increased circulating levels of another biomarker  reflect axonal damage due to traumatic brain injury, inflammatory processes, or cerebrovascular diseases7. Recent trials of antibody therapies that target beta-amyloid indicate that delaying cognitive decline in patients with AD may be possible, although the risk of adverse side effects  is significant12. These results nevertheless suggest therapies targeting specific disease-driving pathologies identified with clinical testing could be achievable. However, further research is needed to reduce risk associated with these treatments and discover new modifiable risk factors for dementia.Recent advances in neuroimaging and blood-based biomarkers have improved dementia diagnosis and monitoring of disease progression13. The pathologies that underlie the relationship between circulating adropin levels and cognition are not known. However, expression profiling of the mRNA encoding adropin in humans and nonhuman primates and measurements of adropin protein expression in mice suggest it is abundant in the nervous system16. In all three species, adropin expression clusters with gene networks implicated in neurodegenerative conditions15. For example, in human postmortem brain samples strong positive correlations are observed between adropin expression and gene networks involved in mitochondrial function, synaptic plasticity, and cerebrovascular function14. These processes are relevant to maintaining brain health during aging17.The secreted peptide adropin could be a novel risk indicator for accelerated cognitive decline. Low circulating levels of adropin associated with accelerated cognitive decline in community-dwelling old individuals in the Multidomain Alzheimer’s Preventive Trial (MAPT)18, while adropin treatments improve cognition in 18-month-old male mice19. This outcome potentially involves direct and indirect actions on neurons. Adropin is neurotrophic when applied directly to cultured neurons14, while also preserving cerebrovascular function in situations of ischemia22. Adropin could thus support synaptic plasticity in the brain while also preventing neurovascular diseases thought to contribute to cognitive decline23. However, whether results from mouse studies will translate to humans has yet to be determined.Studies using rodent models support the hypothesis that high adropin activity preserves cognitive ability in aging. Adropin expression in the mouse and rat brain declines with aging13. The primary objective of the current study was, therefore to determine whether the relationship between circulating adropin and cognition replicates in different populations. A secondary objective was to further investigate the expression profile of the Energy Homeostasis Associated (ENHO) mRNA transcript that encodes adropin in the human nervous system.To date, there has been only one study investigating the relationship between circulating adropin concentrations and cognitive impairment in humansMean age, sex, BMI, and serum adropin concentrations of the subjects used for this study are shown in Supplementary Table p = 0.014, 95% CI 0.629-0.948, n = 338). Several studies have observed relationships between circulating adropin and indices of obesity and dysregulated glucose and/or lipid metabolism25. A follow-up analysis that included additional covariates that might affect circulating adropin levels or cognition . Of note, weak correlations were observed between serum levels of adropin and adiponectin , fructosamine , and TG . However, including these covariates did not affect the relationship between adropin and poor cognition  (Table p < 0.001) .Serum adropin concentrations did not correlate with circulating markers of inflammation (data not shown). High neurofilament light chain (NfL) levels can indicate increased risk of dementia14. We used snRNA-seq data from the Seattle Alzheimer’s Disease Brain Cell Atlas to compare relative expression levels and fraction of cells within each population in the human middle temporal gyrus (MTG). The data is from a reference neurotypical population of males and females   ; however, the relative level of expression is lower compared to astrocytes. There appears to be a reduced expression in the older cohort, irrespective of age, sex, and dementia status  Fig.  and an o84) Fig. 27. This age Fig. . Oligodeage Fig. . A few pp = 0.108).In astrocytes isolated from human donors, ENHO expression levels also appear to decline with donor age Fig. . While a18.The results from snRNA-seq and cultured astrocytes nevertheless suggest that ENHO expression declines with aging. A similar effect has been reported at the level of adropin protein expression in cortical lysates from shorter-lived rodent models15. Correlation coefficients were calculated by comparing all transcripts against ENHO or donor age. Comparison of the correlations between all transcripts and either ENHO or donor age suggested an interaction  or an R < −0.7 paired with donor age (1627 genes). There was significant overlap between the population (826 genes)  suggest ENHO expression is suppressed by the TLR3 agonist Poly I:C, and by TNFα . Adropin is however not regulated by hypoxia in astrocytes isolated from mice or human brain samples 22. Moreover, experiments using C57BL/6J mice suggest high adropin expression prevents or delays cognitive decline with natural aging14 or obesity-related metabolic dysregulation 28. This could involve a direct trophic action to support neuronal networks14. However, adropin could also act on the brain vasculature to preserve blood-brain barrier integrity and reduce risk of ischemia22. Further studies are needed to determine the pathologies underlying the association between circulating adropin levels and cognition.The rationale for this study was based on our previous reports using human expression profiling data and mouse models of aging13. In that study, circulating adropin concentrations did not correlate with cognitive ability at the time of sampling, but correlated with subsequent cognitive decline. The reasons for the disparity are not clear, but it is important to note the differences between the two studies. The MAPT study involved older Europeans who had access to universal healthcare. In contrast, the AAH involved self-reported African Americans living in the inner city or suburban St. Louis who had likely experienced racial disparities in health care29. The MAPT used a comprehensive analysis of cognitive function, while the current study was limited to the MMSE and ANT. Indeed, a weakness of the current study is that it only used two cognitive tests. The current study was also not designed to investigate cognitive decline. While suggesting an association between serum adropin levels and cognition, the long-term clinical significance with respect to risk of further cognitive decline in younger cohorts are not known and require further study.The results from this study are a significant extension of our analysis of circulating adropin in the MAPT study14. The current results from the analysis of snRNA-seq data indicate a similar distribution in the brain. These results further suggest that astrocytes are a major site of ENHO expression in the human brain. A caveat is that the current study was limited to one region of the brain (the MTG). It is possible that the distribution between cell types differs between brain regions. Further examination of the distribution of adropin between cell-types within different brain regions will be needed to support the current findings.Using the exploratory resources from the Seattle Alzheimer’s Disease Brain Cell Atlas consortium, we investigated the distribution of ENHO expression in specific cell population in the MTG. We had previously observed relatively high ENHO expression in mature astrocytes compared to other cell populations  maintained in culture media after isolation from human brain samples31. In a diurnal NHP (the baboon), brain adropin expression expressed as fragments per kilobase of transcript per million reads mapped, or FPKM) is orders of magnitude higher relative to non-neural tissues and exhibits a circadian profile with peaks during the daytime15. Circulating adropin concentrations in another NHP model, the rhesus macaque, also appear to exhibit a diurnal profile with higher levels in the daytime15. Collectively, these results suggest that adropin could be a circadian-controlled neuropeptide, with levels in the circulation reflecting expression in the nervous system. However, further study of the source of circulating adropin are needed. It is however important to note that comparison of RNA-seq data between cell and tissue types should be interpreted with caution. Expression levels reported at FPKM or TPM (transcripts per million) don’t account for differences in RNA content between cell- and tissue types32. Moreover, for human tissue samples the variability in interval between death and tissue preservation can affect both RNA quality and yield33.The source(s) of circulating adropin remains to be identified. The brain and (to lesser degree) liver have been identified as major sites of expression1–76 is a prohormone with a signal peptide (adropin1–33) and a secreted peptide (adropin34–76)30. Indeed, adropin is often described as a liver-secreted “hepatokine”34. However, a later study refuted the finding that adropin is secreted, describing instead a membrane-bound protein primarily expressed in the brain16. This conclusion is supported by data from AlphaFold’s transmembrane protein structure database, which predicts a transmembrane region near the N-terminus. We have observed adropin secretion by human iPSCs can be detected using the enzyme immunoassay used for this study in conditioned media . This result is predicted based on the results from experiments that used an C-terminal epitope-tagged adropin fusion protein which indicated a portion of the prohormone is secreted into the media by cultured cells, and into the mouse circulatory system when expressed in the liver30. These results suggest an as-yet unidentified mechanism for releasing a portion of the adropin prohormone from the cell.The initial studies investigating circulating levels of adropin resulted from data suggesting adropinA strength of the brain cell atlas dataset is the involvement of older subjects with a range of AD pathology. While ENHO expression appears to decline with aging, expression does not appear to be markedly different between people with or without dementia. Indeed, comparisons between the 84 older subjects and the reference group suggests that age may have an inhibitory effect on expression.18. Preventing this decline, or treatment using synthetic adropin peptide, improves spatial learning and memory14. However, whether the decline is sufficient per se to cause cognitive impairment is not known. While studies have examined how adropin therapy affects cognition in mouse models, there have been no studies to determine whether deficiencies in adropin expression accelerate cognitive decline in aging.In shorter-lived mice and rats, adropin protein levels in the brain decline between 3 and 18 months of ageENHO expression in cultured human astrocytes also correlates inversely with donor age, which is consistent with the results from the analysis of expression in the MTG using snRNA-seq. This relationship appears to correlate with changes in metabolic activity. Specifically, ENHO expression adjusted for donor age correlates positively with cellular pathways involved in energy-demanding cytosolic processes involved in macromolecule synthesis and turnover. ENHO expression also correlates with the mitochondrial process needed to provide the energy for these processes. High adropin expression in young astrocytes thus appears to correlate with higher metabolic activity and energy demand, with energy production presumably required for the synthesis of macromolecules .14. High adropin expression in the brain may, therefore, reflect relatively high levels of metabolic activity. Experiments using mice suggest that this relationship could be causal, as adropin treatment enhances the expression of similar pathways in the mouse brain14. Further studies are clearly needed to determine whether circulating adropin levels correlate with brain ENHO expression and with pathways involved in energy utilization.This result is important, as it is consistent with the relationships observed between ENHO expression and gene clusters in RNA-seq data derived from human post-mortem brain samples18. Neuroinflammation is one of the key mechanisms identified in neurodegenerative diseases36. Here we observed evidence of a direct response of ENHO transcript expression in astrocytes to TNFα and a TLR3 agonist. While the effect is observed in astrocytes from human and mouse donors, the effect appears more robust in the latter. It is important to note that the astrocytes used for this study were isolated from developing brains37. The relevance to the conditions observed in the aginh brain is therefore unclear. However, the results are significant in suggesting a direct inhibitory effect of inflammatory signals on adropin expression in astrocytes.In rodent models of aging, a decline in adropin protein levels is observed in brain lysates28. Adropin-deficient mice are more susceptible to cerebrovascular ischemia21. However, experiments using mouse models are needed to explore the relationship between low adropin expression and cognitive decline driven by other risk factors for dementia. Furthermore, the relationship if any between adropin expression in the brain of young to middle-aged people with cognitive functions is not known, and was not addressed in this study.It important to note that ENHO expression was not lower in older people diagnosed with dementia compared to those who did not exhibit dementia. The expression profile of ENHO in older people categorized by BRAAK staging also indicated no decline with increasing severity. This suggests that low ENHO expression per se is unlikely to be a primary driver of dementia in older individuals. Rather, low adropin expression levels in the brain, and levels of circulating adropin, could facilitate disease progression. In this model, reduced neuroprotection due to low expression would have less constraint on disease progression driven by other genetic and environmental risk factors. This model is consistent with data from experiments using mice that over express adropin38. The study population therefore does not include late middle-aged people with dementia. The ceiling effect observed with the MMSE is also a limitation; it has a maximum score of 30 which was achieved by nearly a third of the subjects included in the study. And as already stated, only two tests were used to assess cognitive function, and there was some inconsistency in the correlations between the two tests. These results should therefore be considered preliminary. Additional studies are clearly needed to explore the relationships between circulating adropin concentrations and risk of dementia.There are limitations to the current study. These include the use of a cohort housed in a single geographic location. The study limited to a single racial group (African Americans), albeit from two socioeconomically diverse geographic areas. Another limitation was that the inclusion criteria for the AAH study included a MMSE score of ≥16In summary, the results of the current study indicate that low circulating adropin concentrations in late middle-aged people associate with poor cognitive function. Further studies are needed to determine whether circulating adropin concentrations correlate with risk for cognitive decline with aging and impaired glucose homeostasis.40. Recruitment used a multi-stage probability sampling methodology aimed at selecting approximately equal numbers of participants from inner-city and near suburban neighborhoods northwest of Saint Louis City. The study procedures were reviewed and approved by the Institutional Review Board at Saint Louis University and were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and later amendments. All participants provided written consent for study, including blood draw.AAH was a population-based, community-dwelling cohort of 998 self-identified African Americans in 2000–2001 in the Saint Louis metropolitan area40. Participants initially completed in-home interviews and assessments at baseline, and at years 3 and 9 the recruitment proportion (participants/enumerated eligible persons) was 76%. Self-reporting bias was minimized using validated and reliable criteria for collecting self-reported data. A subset of participants agreed to donate blood; serum samples were stored at −80 °C for laboratory analyses. This was a community-based study; fasting was not required at the time of blood collection to encourage participation. Age and years of education are self-reported. For age, participants were asked to report their age and date of birth; mismatches between the two answers resulted in a query for clarification.Inclusion criteria for AAH included self-reported Black or African American race; birth dates between 01/01/1936 and 12/31/1950; standardized Mini-Mental Status Examination (MMSE) scores ≥ 16; and willingness to sign an informed consent formThe current study established baseline fed serum adropin concentrations for 352 of the participants for which serum was still available. These values were compared to baseline cognitive data and serum markers of metabolic homeostasis and immune function.41. The MMSE is comprised of 11-questions that test five areas of cognitive function , with a maximum score of 30. There is a ceiling effect with the MMSE test which does not occur in the ANT test, which is a limitation of this approach. Out of 352 subjects, 142 had an MMSE score of 30.Cognitive performance was assessed by the MMSE and one-minute animal naming test of verbal fluency (ANT) performed at the same time during the at-home evaluations. The MMSE is a screening tool for detecting cognitive deficits in dementia and delirium43. The ANT assesses memory recall and verbal fluency43.A composite cognitive test score was calculated using the sum of the Z scores for the results of both tests. MMSE scores of ≤23 or ANT scores of ≤15 predict risk for dementiaρ = 0.333, p < 0.001, n = 338)   for the composite score (MMSE + ANT_worst_quint)  and arbitrarily assigned a value of 0.15 ng/ml . Values > 8.2 ng/ml were described as “high” and arbitrarily assigned a value of 8.5 ng/ml (n = 2).Laboratory analyses used blood collected from a subset of AAH participants within ~2 weeks of the at-home assessment of mental status. Serum adropin concentrations were measured using an enzyme immunoassay kit from Phoenix Pharmaceuticals, Inc. (cat. no. EK-032-35) following the manufacturer’s protocol. Assay sensitivity reported by the manufacturer is 0.3 ng/ml, with a linear range from 0.3 to 8.2 ng/ml. Pilot experiments determined a 1:5 dilution of serum produced values within the linear range. Values < 0.3 ng/ml were described as “low” . For samples with %CV > 20, the “outlier” was removed. Data from triplicates with no clear outlier (5 samples) were excluded. The mean, median, and standard deviation (SD) for the 347 samples used in the analysis were 3.17, 3.11, and 1.35 ng/ml, respectively.45. Briefly, fructosamine was measured as previously described46. The fructosamine test measures average glucose levels over 2–3 weeks prior to testing, and can be used in situations where the hemoglobin A1C test is not reliable 47. Fructosamine values have also been reported to more consistently correlate with continuously monitored glucose values than A1C47. As detailed medical evaluations were not available, fructosamine values were used to estimate of averaged glucose levels over multiple days. Fructosamine values in people without diabetes range from 175 to 285 μmol/L; values of 286 μmol/L or higher indicate impaired glucose homeostasis and elevated blood glucose levels.The procedures used to measure serum indices of metabolic control and inflammation have been described previously48. IL-6 circulates bound to sIL-6R, and the levels of sIL-6R are increased in inflammatory states48. The levels of sIL-6R were determined using ELISA . High levels of other soluble cytokine receptors and C-reactive protein (CRP) were previously shown to associate with poor physical performance in the AAH49. ELISA kits  were used for measuring soluble Tumor Necrosis Factor Receptor-1 (sTNFR1)  and soluble Tumor Necrosis Factor Receptor-2 (sTNFR2) . CRP was measured using a High-Sensitivity Enzyme Immunoassay (hsCRP ELISA) .The soluble Interleukin-6 Receptor (sIL-6R) predominantly results from cleavage from cell-surface IL-6R, and is involved in IL-6 trans-signaling, a process which results in most cell-types becoming responsive to IL-6http://portal.brain-map.org/explore/seattle-alzheimers-disease)27. ENHO expression was compared in single nuclei isolated from the MTG of 84 older individuals  and a younger neurotypical reference group .ENHO expression in human brain samples was assessed using data from the Seattle Alzheimer’s Disease Cell Atlas consortium  used an immunopanning method to isolate astrocytes from juvenile (8–18 y of age) and adult (21–63 y of age) human brain tissue samples extracted during neurological surgery51. The samples were from the healthy temporal lobe cortices and were rapidly processed following surgical removal. For the “immunopanning” protocol, single-cell suspensions of dissociated tissues were incubated sequentially in a series of antibody-coated Petri dishes, with an anti-HepaCAM antibody used to bind and extract astrocytes.To investigate the regulation of ENHO expression in cultured astrocytes, RNA sequencing (RNA-seq) data from two published experiments was downloaded from the Gene Expression Omnibus (GEO)51 were used to identify gene networks correlating with ENHO expression in human astrocytes. These were identified using a paired partial correlation analysis as previously described15; donor age was used as a covariate in calculating the correlation matrix. Only genes with a mean FPKM of >1 were included in the analysis. Correlation coefficients of >0.7 or <−0.7 were used as selection criteria. The ToppGene Suite was used to identify gene networks overrepresented in genes identified as correlating positively or negatively with the ENHO transcript encoding adropin. Li et al. (GSE147870) applied a similar protocol to extract astrocytes from human and mouse brains37.The RNAseq data from the study of Zhang et al.U test, two-sided). When needed, data from ANCOVA adjusted for covariates (indicated in the text) are reported as estimated marginal means ± standard error. Binomial logistic regression was used to estimate the relationship serum adropin concentrations and risk of poor cognitive performance. Poor cognitive performance was defined as scoring in the low quintile for the composite score (MMSE + ANT_worst_quint). Modeling of the relationships between serum adropin concentrations and indices of glycemic control , lipid metabolism, and inflammation used Spearman’s correlation coefficient (ρ).Data were analyzed using IBM SPSS Statistics version 19.0 . Unadjusted data are presented as mean ± standard deviation. Comparisons of unadjusted data between two groups  used a nonparametric test (Mann-Whitney Further information on research design is available in the Supplementary datasetSupplementary informationReporting summary


Klebsiella pneumoniae. The PK, safety, and efficacy data of MV in adults support study in pediatrics.The worldwide spread of serine carbapenemases threatens carbapenems. VABOMERE (combination of meropenem and vaborbactam (MV), is a new class of beta-lactamase inhibitors including inhibition of Phase 1, open-label, dose-finding study. Pediatric subjects, 3 mos. to < 18 yrs already on antibiotics received a single-dose weight based infusion of MV over 3 hr. Blood samples were drawn pre-dose, 3,4, and 6 hr. for PK parameters. Population PK model included weight as a covariate. Safety assessments included AEs, vital signs, safety labs, physical exams, infusion tolerance, ECG. A DSMB reviewed safety and PK data before enrolling next cohort.MV was well-tolerated and safe in all age groups. Clearance per kg body weight of both M and V increased with decreasing body weight over all age groups suggesting an allometric relationship.0-8 efficacious in adult trials ranges of 91.7-513 mg•hr/L (meropenem) and 131-494 mg•hr/L (vaborbactam) were achieved in all pediatric cohorts.Targeted AUCPaula M. Bokesch, MD, Melinta Therapeutics: Advisor/Consultant Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Randall K. Hoover, Ph.D., Melinta Therapeutics: Advisor/Consultant Sandra McCurdy, MS, Melinta Therapeutics: Employee


With the gradual depletion of shallow oil and gas, deep oil and gas has become the focus of development. However, deep formations generally face the challenge of high-temperature and high-salinity, and drilling fluid agents are prone to failure, leading to drilling fluid intrusion into the formation that can cause serious drilling accidents such as well bore collapse. For this, a styrene-based nano-microsphere (SSD) modified with amphoteric ions was developed, with a particle size of 228 nm which could resist temperatures up to 200 °C and sodium chloride (NaCl) up to saturation. SSD has significant salt-responsive properties and its aqueous dispersion becomes transparent with increasing salinity. The SSD provided superior plugging performance in solutions containing NaCl, with a core plugging efficiency of 95.2%, and it was significantly better than the anion-modified microspheres. In addition, in drilling fluids under high temperature and high-salinity conditions, the SSD promotes particle gradation of drilling fluids and improves the zeta potential through its own plugging and synergistic effect with clay, which significantly improves the comprehensive performance of drilling fluids, such as stability, rheological performance, and filtration reduction performance. The development of SSD provides a new idea for research of high-temperature and high-salinity-resistant drilling fluid agents. At present, oil and natural gas are still one of the most important energy sources in the world ,2,3. WitDrilling fluid is indispensable the drilling process, called the blood of drilling ,13. It fIn order to prevent the drilling fluid from infiltrating and intruding into the formation under high-temperature and high-salinity conditions, and to maintain the stability of the well bore, many countries have adopted the method of plugging the pore space of the formation ,21,22,23Amphoteric polymers with a reverse polyelectrolysis effect are used in drilling fluids because of their excellent salt tolerance properties, which can significantly improve the performance of drilling fluids under high-salinity conditions ,36,37. TSodium styrene sulfonate  and methacryloxyethyl trimethyl ammonium chloride  were purchased from McLean Biochemicals & Technologies Ltd., Shanghai, China. Styrene , and ammonium persulfate (AR) and sodium chloride  were purchased from Sinopharm Chemical Reagent Co., Shanghai, China. Alkylphenol ether sulfosuccinate sodium salt  was provided by Shandong Yusuo Chemical Technology Co., Linyi, China. Bentonite is purchased from Huai’an County Tengfei Bentonite Development Co., Zhangjiakou, China.First, 0.2 g of MS-1 was dissolved into 80 g of deionised water and 10 g of ST, 1 g of SSS, and 1.21 g of DMC were dispersed therein sequentially, and then the dispersion was shear emulsified at 2000 r/min for 10 min. The dispersion was transferred to a flask, which was heated in a water bath at 80 °C, with a stirring speed of 700 r/min, and nitrogen was passed through to evacuate the oxygen. Ammonium persulfate, 0.05 g, was dissolved into 2 mL of deionised water and added drop by drop to the flask after stirring the dispersion for 30 min. After the reaction at constant temperature for 5 h, the resulting white emulsion is the microsphere dispersion SSD. As a comparison, microsphere emulsion SS without DMC monomer was prepared according to the same method.−1 to 4000 cm−1.The microsphere emulsions were purified by soaking them in a dialysis bag (Mw8000) in a sufficient amount of deionized water for 72 h, and then freeze-dried. The structures of the two microspheres were characterised by IR spectrometer  with scanning wavelengths ranging from 400 cmThe microscopic morphology of the microspheres was observed with the aid of a transmission electron microscope  after 100-fold dilution and drying by dropping on a copper grid. The particle size of the microspheres was measured by a particle size analyzer  at the same dilution.The same mass of SSD was added to brines with different concentrations of NaCl (9 g of SSD was added to 100 mL of solution), and the transmittance of SSD dispersions at different concentrations of NaCl was investigated using a visible spectrophotometer .The plugging performance of the microspheres was evaluated using a core expulsion device . The core was made of artificial sandstone, with a length of 5 cm and a diameter of 2.5 cm. The dispersion concentration of the microsphere emulsion was 5%. The pressure transfer experiment was carried out as follows: firstly, the upstream pressure was constant at 3.5 MPa, the peripheral pressure was 5 MPa, and the back pressure was set at 3.5 MPa; then, the experiment was started and the downstream pressure was recorded. After the downstream pressure was constant, the back pressure was deflated, the maximum flow velocity was set to 2 mL/min, and the exclusion was continued for 16 h to evaluate the plugging performance.The basic drilling fluid (DF) was obtained by dispersing 16 g bentonite into 400 g of water, stirring at high speed for 20 min, and then left to stand for 24 h. SSD and NaCl etc. was dispersed into DF according to the quality requirements and stirred at high speed for 20 min to produce the required drilling fluid. Hot rolling was used to seal the drilling fluid in the aging tank tightly. With the fluid in the hot rolling furnace, it was rolled at constant temperature for 16 h; then, taken out after cooling naturally and stirring at high speed for 20 min.The rheological properties of the drilling fluid were tested using a six-speed rotational viscometer  and a Hacker rheometer , respectively.Apparent viscosity (AV) and plastic viscosity were calculated using the formulas:The filtration loss of drilling fluid at a differential pressure of 100 psi over 30 min was determined using a medium-pressure filtration loss meter according to API standards. The mudcake obtained from the filtration loss was dried at 105 °C and observed at 5000× . The stability of the drilling fluid was tested using an emulsion stability analyzer  with a scanning frequency of 5 min/cycle. The particle size distribution of the drilling fluid was measured using a particle size meter . Zeta potential was measured by a potentiostat  and the drilling fluid was diluted at 1:1000.To verify the target products, the copolymers SS and SSD were characterised by FTIR as shown in −1, 3059 cm−1, and 3026 cm−1 are C-H vibrational peaks at different positions on the benzene ring. The three C-C stretching vibrational absorption peaks in the benzene ring are at 1602 cm−1, 1494 cm−1, and 1450 cm−1. The asymmetric and symmetric stretching vibrational absorption peaks of methylene in the polymer chain are found at 2926 cm−1 and 2833 cm−1. The peaks at 1195 cm−1 and 1118 cm−1 are asymmetric and symmetric stretching vibrational peaks of the sulphonic acid group, indicating that sodium styrenesulfonate was involved in the polymerization. Notably, the peak at 1730 cm−1 is a stretching vibration peak of C=O in the ester group, which indicates that the preparation of SSD contains DMC. In addition, there are no obvious peaks of unreacted vinyl in the spectrum, and both SS and SSD are target products and fully reacted.The FTIR spectra of the two polymeric microspheres are shown in The structures of the two copolymers were further characterised by thermal gravimetric analysis, as shown in The morphology of the microspheres SS and SSD are shown in When a beam of light illuminates a medium containing dispersed particles, light transmission, light scattering, and light reflection will occur, depending on the size of the particles. If the particles of the dispersed medium are much larger than the wavelength of the incident light, light reflection occurs and the medium is opaque. Until the diameter of particles decreases to less than the wavelength of light, then light will scatter and the medium becomes transparent. When the particle size is much smaller than the wavelength, light transmission occurs and the solution is completely transparent. For SSD, its aqueous dispersion system showed different transmittance with different salt concentrations. Under the irradiation of light at 600 nm, the transmittance of SSD dispersion was improved with increasing NaCl concentration, which could increase from 19.36% to 30.68% as The plugging performance of the microspheres under different dispersion conditions was tested using core pressure transmission and core plugging experiments respectively, as shown in The rheological properties of the drilling fluid are of critical importance. They are related to the rock-carrying properties of the drilling fluid, as shown in Further, the effect of microspheres on the rheological properties of drilling fluids was evaluated using composite modulus (G*) tests. The composite modulus can reflect the structural strength of the reticulation in the drilling fluid, allowing the evaluation of its suspension stability and rock-carrying capacity . The G* in the curve are constant and then suddenly decrease, and the value of τ at this turning point represents the yield stress of the drilling fluid. Under the conditions of room temperature and saturated NaCl, both SS and SSD can increase the yield value of drilling fluids, and the ability of SSD is significantly better than that of SS. After hot rolling at 200 °C, the strength of the grid structure in the drilling fluid decreases, as does the yield value. At this time, only SSD substantially increased the yield value of DF. This indicates that SSD has excellent resistance to high-temperature and salt, which can improve the structural strength and stability of drilling fluids under the conditions of high-temperature and high-salinity.Filtration loss reduction is another important property of drilling fluids, which is aimed at preventing water from entering the formation, maintaining the stability of the well bore and protecting the drilling safety. The drilling fluid can maintain a low fluid loss without salt, while with the addition of NaCl, the fluid loss of the drilling fluid increases abruptly. This loss of drilling fluids is caused by the destructive effect of NaCl on the diffuse double layer of clay, which leads to the reduction in the thickness of the clay hydration film, weaker interaction between particles, and reduced densification of the mud cake. High-temperature will exacerbate damage to the clay, as shown in TSI is an evaluation of the stability of the entire dispersion system; the larger its value, the more unstable the system. Both SS and SSD can improve the stability of drilling fluids with NaCl at room temperature, as shown in The microscopic morphology of the mud cake of DF after hot rolling at 200 °C and saturated NaCl is shown in The mechanisms of SSD in drilling fluid was further investigated using particle size analysis and zeta potential analysis. As shown in The mechanism of SSD in drilling fluids was revealed through a series of experiments, as shown in (1) A new amphoteric ion-modified, styrene-based nano-microsphere, SSD, was developed with a particle size of 228 nm.(2) SSD shows salt-responsive properties; its surface molecular chains gradually stretch and solution transparency increases with increasing salinity, thus providing a better ability to plug rock pores.(3) Compared to general styrene-based microspheres modified with anions, SSD has an advantage in improveding the performance of drilling fluids at high-temperature and high-salinity conditions. It can better synergize with clay to improve the suspension and dispersion stability of the drilling fluid, improve the quality of the mud cake, and reduce fluid loss.