Superdiffusive Rotation of Interfacial Water on Noble Metal Surface.

Interfacial water on a metal surface acts as an active layer through the reorientation of water, thereby facilitating the energy transfer and chemical reaction across the metal surface in various physicochemical and industrial processes. However, how this active interfacial water collectively behaves on flat noble metal substrates remains largely unknown due to the experimental limitation in capturing librational vibrational motion of interfacial water and prohibitive computational costs at the first-principles level. Herein, by implementing a machine-learning approach to train neural network potentials, we enable performing advanced molecular dynamics simulations with ab initio accuracy at a nanosecond scale to map the distinct rotational motion of water molecules on a metal surface at room temperature. The vibrational density of states of the interfacial water with two-layer profiles reveals that the rotation and vibration of water within the strong adsorption layer on the metal surface behave as if the water molecules in the bulk ice, wherein the O-H stretching frequency is well consistent with the experimental results. Unexpectedly, the water molecules within the adjacent weak adsorption layer exhibit superdiffusive rotation, contrary to the conventional diffusive rotation of bulk water, while the vibrational motion maintains the characteristic of bulk water. The mechanism underlying this abnormal superdiffusive rotation is attributed to the translation-rotation decoupling of water, in which the translation is restrained by the strong hydrogen bonding within the bilayer interfacial water, whereas the rotation is accelerated freely by the asymmetric water environment. This superdiffusive rotation dynamics may elucidate the experimentally observed large fluctuation of the potential of zero charge on Pt and thereby the conventional Helmholtz layer model revised by including the contribution of interfacial water orientation. The surprising superdiffusive rotation of vicinal water next to noble metals will shed new light on the physicochemical processes and the activity of water molecules near metal electrodes or catalysts.

Mode-locking and wavelength-tuning of a NPR fiber laser based on optical speckle.

Passively mode-locked fiber lasers based on nonlinear polarization rotation (NPR) have been widely used due to their ability to produce short pulses with high peak power. Nevertheless, environmental perturbations can influence the mode-locked state, making it a challenge for the practical implementation. Therefore, researchers are searching for assessment criteria to quickly assist and maintain mode-locking of NPR fiber lasers. Speckle patterns containing spectral information can be generated when the laser transmits through a scattering medium, which can serve as indicators of the mode-locked state. The mode-locked regions are confined to the area close to the minimum texture contrast of speckle patterns. Based on these characteristics, we manually simulate the automatic mode-locking (AML). In addition, we utilize convolutional neural networks (CNNs) to recognize speckle patterns of wavelength tunable lasers and determine the center wavelength.

Yb-doped mode-locked fiber laser with a hybrid structure of NPR and a Lyot filter as the saturable absorber.

Passively mode-locked fiber lasers based on a nonlinear polarization rotation (NPR) have attracted much attention due to their ability to generate short pulses with wide spectra and high peak power. However, environmental perturbations can easily cause the lasers to lose the mode-locked state and make it a challenge for practical application. The aim of this research is to improve the laser stability by inserting a Lyot filter into the mode-locked laser cavity. The experimental results indicate that the mode-locked state can be maintained when the radius of the fiber loop is changed from 7.5 to 1.5 cm, while the signal-to-noise ratio of the fundamental frequency remains almost the same. The tunability of the output power can be achieved by adding a half-wave plate (HWP) in the laser cavity without changing the pump power, while the mode-locked state remains stable. By adjusting the angle of the HWP2, the output power can be adjusted from 3.36 to 66.5 mW at repetition rate of 29.7 MHz.

Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.

Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders, which are also manifested by wolfram syndrome (WS). Whether and how the causative gene WFS1 deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids, WFS1-deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes. WFS1 deficiency in neurons autonomously delays neuronal differentiation with altered expressions of genes associated with psychiatric disorders, and impairs neurite outgrowth and synapse formation with elevated cytosolic calcium. Intriguingly, WFS1 deficiency in astrocytes decreases the expression of glutamate transporter EAAT2 by NF-κB activation and induces excessive glutamate. When co-cultured with wildtype neurons, WFS1-deficient astrocytes lead to impaired neurite outgrowth and increased cytosolic calcium in neurons. Importantly, disrupted synapse formation and function in WFS1-deficient cerebral organoids and impaired neurite outgrowth affected by WFS1-deficient astrocytes are efficiently reversed with Riluzole treatment, by restoring EAAT2 expression in astrocytes. Furthermore, Riluzole rescues the depressive-like behavior in the forced swimming test and the impaired recognition and spatial memory in the novel object test and water maze test in Wfs1 conditional knockout mice. Altogether, our study provides novel insights into how WFS1 deficiency affects synapse formation and function, and offers a strategy to treat this disease.

Co-inoculation of rhizobia and AMF improves growth, nutrient uptake, and cadmium resistance of black locust grown in sand culture.

Rhizobia and arbuscular mycorrhizal fungi (AMF) are symbiotic microorganisms important for plants grown in nutrient-deficient and heavy metal-contaminated soils. However, it remains unclear how plants respond to the coupled stress by heavy metal and nitrogen (N) deficiency under co-inoculation. Here, we investigated the synergistic effect of Mesorhizobium huakuii QD9 and Funneliformis mosseae on the response of black locust (Robinia pseudoacacia L.) grown in sand culture to cadmium (Cd) under N deficiency conditions. The results showed that single inoculation of AMF improved the growth and Cd resistance of black locust, co-inoculation improved the most. Compared to non-inoculated controls, co-inoculation mediated higher biomass and antioxidant enzyme activity, reduced oxidative stress, and promoted nodulation, mycorrhizal colonization, photosynthetic capacity, and N, P, Fe and Mg acquisition when exposed to Cd. This increase was significantly higher under N deficiency compared to N sufficiency. In addition, the uptake of Cd by co-inoculated black locust roots increased, but Cd translocation to the above-ground decreased under both N deficiency and sufficiency. Thus, in the tripartite symbiotic system, not merely metabolic processes but also Cd uptake increased under N deficiency. However, enhanced Cd detoxification in the roots and reduced allocation to the shoot likely prevent Cd toxicity and rather stimulated growth under these conditions.

Aberrant HO-1/NQO1-Reactive Oxygen Species-ERK Signaling Pathway Contributes to Aggravation of TPA-Induced Irritant Contact Dermatitis in Nrf2-Deficient Mice.

NF-erythroid 2-related factor 2 (Nrf2) is a major transcription factor to protect cells against reactive oxygen species (ROS) and reactive toxicants. Meanwhile, Nrf2 can inhibit contact dermatitis through redox-dependent and -independent pathways. However, the underlying mechanisms of how Nrf2 mediates irritant contact dermatitis (ICD) are still unclear. In this article, we elucidated the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute ICD. Our study demonstrated that the ear thickness, redness, swelling, and neutrophil infiltration were significantly increased, accompanied by increased expression of inflammatory cytokines (IL-1α, IL-1ß, IL-6, etc.) and decreased expression of antioxidant genes (HO-1 and NQO1) in Nrf2 knockout mice. Moreover, ERK phosphorylation was elevated in mouse embryonic fibroblasts (MEFs) from Nrf2 knockout mouse. Inhibition of ERK significantly alleviated TPA-induced cutaneous inflammation and ROS accumulation in MEFs derived from mouse. Conversely, ROS scavenging inhibited the ERK activation and TPA-induced inflammation in MEFs. Taken together, the findings illustrate the key role of the Nrf2/ROS/ERK signaling pathway in TPA-induced acute ICD.

Orientational dynamics of the water layer adjacent to Au surface accelerated by polarization effect.

The orientation and rearrangement of water on a gold electrode significantly influences its physicochemical heterogeneous performance. Despite numerous experimental and theoretical studies aimed at uncovering the structural characteristics of interfacial water, the orientational behavior resulting from electrode-induced rearrangements remains a subject of ongoing debate. Here, we employed molecular dynamics simulations to investigate the adaptive structure and dynamics properties of interfacial water on Au(111) and Au(100) surfaces by considering a polarizable model for Au atoms in comparison with the non-polarizable model. Compared to the nonpolarizable systems, the polarization effect can enhance the interaction between water molecules and the gold surface. Unexpectedly, the rotational dynamics directly associated with the orientational behavior of water adjacent to the gold surface is accelerated, thereby reducing the hydrogen bond lifetime. The underlying mechanism for this anomalous phenomenon originates from the polarization effect, which induces the attraction of the positive hydrogen atoms to the surface by the negative image charge. This leads to a change in orientation that disrupts the hydrogen bonds in the first water layer and subsequently accelerates reorientation dynamics of water molecules adjacent to the gold surface. These results shed light on the intricate interplay between polarization effects and water molecule dynamics on metal surfaces, establishing the foundation for the rational regulation of the orientation of interfacial water.

Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell-Cell Interactions.

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell-cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell-cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. This study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.

Preserving Structurally Labile Peptide Nanosheets After Molecular Functionalization of the Self-Assembling Peptides.

A significant challenge in creating supramolecular materials is that conjugating molecular functionalities to building blocks often results in dissociation or undesired morphological transformation of their assemblies. Here we present a facile strategy to preserve structurally labile peptide assemblies after molecular modification of the self-assembling peptides. Sheet-forming peptides are designed to afford a staggered alignment with the segments bearing chemical modification sites protruding from the sheet surfaces. The staggered assembly allows for simultaneous separation of attached molecules from each other and from the underlying assembly motifs. Strikingly, using PEGs as the external molecules, PEG400 - and PEG700 -peptide conjugates directly self-associate into nanosheets with the PEG chains localized on the sheet surfaces. In contrast, the sheet formation based on in-register lateral packing of peptides does not recur upon the peptide PEGylation. This strategy allows for fabrication of densely modified assemblies with a variety of molecules, as demonstrated using biotin (hydrophobic molecule), c(RGDfK) (cyclic pentapeptide), and nucleic acid aptamer (negatively charged ssDNA). The staggered co-assembly also enables extended tunability of the amount/density of surface molecules, as exemplified by screening ligand-appended assemblies for cell targeting. This study paves the way for functionalization of historically challenging fragile assemblies while maintaining their overall morphology.

Engineering Co-N-Cr Cross-Interfacial Electron Bridges to Break Activity-Stability Trade-Off for Superdurable Bifunctional Single Atom Oxygen Electrocatalysts.

Atomically dispersed metal-nitrogen-carbon (M-N-C) catalysts have exhibited encouraging oxygen reduction reaction (ORR) activity. Nevertheless, the insufficient long-term stability remains a widespread concern owing to the inevitable 2-electron byproducts, H2O2. Here, we construct Co-N-Cr cross-interfacial electron bridges (CIEBs) via the interfacial electronic coupling between Cr2O3 and Co-N-C, breaking the activity-stability trade-off. The partially occupied Cr 3d-orbitals of Co-N-Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co-OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co-N-Cr CIEBs suppress the two-electron ORR process and approach the apex of Sabatier volcano plot for four-electron pathway simultaneously. As a proof-of-concept, the Co-N-Cr CIEBs is synthesized by the molten salt template method, exhibiting dominant 4-electron selectively and extremely low H2O2 yield confirmed by Damjanovic kinetic analysis. The Co-N-Cr CIEBs demonstrates impressive bifunctional oxygen catalytic activity (▵E=0.70 V) and breakthrough durability including 100 % current retention after 10 h continuous operation and cycling performance over 1500 h for Zn-air battery. The hybrid interfacial configuration and the understanding of the electronic coupling mechanism reported here could shed new light on the design of superdurable M-N-C catalysts.

Peptide Stapling by Crosslinking Two Amines with α-Ketoaldehydes through Diverse Modified Glyoxal-Lysine Dimer Linkers.

α-Ketoaldehydes play versatile roles in the ubiquitous natural processes of protein glycation. However, leveraging the reactivity of α-ketoaldehydes for biomedical applications has been challenging. Previously, the reactivity of α-ketoaldehydes with guanidine has been harnessed to design probes for labeling Arg residues on proteins in an aqueous medium. Herein, a highly effective, broadly applicable, and operationally simple protocol for stapling native peptides by crosslinking two amino groups through diverse imidazolium linkers with various α-ketoaldehyde reagents is described. The use of hexafluoroisopropanol as a solvent facilitates rapid and clean reactions under mild conditions and enables unique selectivity for Lys over Arg. The naturally occurring GOLD/MOLD linkers have been expanded to encompass a wide range of modified glyoxal-lysine dimer (OLD) linkers. In a proof-of-concept trial, these modular stapling reactions enabled a convenient two-round strategy to streamline the structure-activity relationship (SAR) study of the wasp venom peptide anoplin, leading to enhanced biological activities.

Atomically Dispersed p-Block Aluminum-Based Catalysts for Oxygen Reduction Reaction.

The main group metals are commonly perceived as catalytically inert in the context of oxygen reduction reactions (ORR) due to the delocalized valence orbitals. Regulating the local environment and structure of metal center coordinated by nitrogen ligands (M-Nx) is a promising approach to accelerate catalytic dynamics. Herein, we, for the first time, report the atomically dispersed Al catalysts coordinated with N and C atoms for 4-electron ORR. The axial coordinated pyrrolyl N group (No) is constructed in the Al-N4-No moiety to regulate the p-band structure of Al center, effectively steering the local environment and structure of the square planar Al-N4 sites, which typically exhibit too strong interaction with ORR intermediates. The dynamic covalency competition of axial Al-No and Al-O bonding could endow the Al center with moderate hybridization between Al 3p orbital and O 2p orbital, alleviating the binding energy of ORR intermediates. The as-prepared Al-N4-No electrocatalyst exhibits excellent ORR activity, selectivity, and durability, along with the rapid kinetics as demonstrated by in situ Raman spectroscopy. This work offers a fundamental comprehension of the fine regulation on p-band and guides the rational design of main-group metal-based single atom catalysts.

Ultrafast vortex arrays generated from a mode-locked oscillator with dispersion management.

Herein, we demonstrate the generation of optical vortex arrays pulses using a Sagnac common-path interferometric vortex generator. Hermite-Gaussian (HG) modes with different orders are initially obtained from a SESAM mode-locked laser in the positive dispersion regime. Then, in the interferometric vortex generator, by controlling the phase difference and sheering displacement between two HG modes, optical vortex pulses with different numbers of phase singularities are generated through superposition. The generated HG10 mode has a pulse width of 2 ps and maximum energy of 0.75 nJ. One-dimensional vortex arrays and triangular vortex arrays are also generated, which are formed by HGm0 and HG0n modes, respectively. This work has potential applications in the massive manipulation of microparticles, optical communication, and so on.

Optical design of a reflective double-grating spectrometer to detect one branch in the pure rotational Raman spectrum of N2.

This paper presents the optical design of a high-resolution double-grating spectrometer for extracting the multiple lines in the Stokes or anti-Stokes branch of the pure rotational Raman spectra of nitrogen. The spectrometer is composed of collimating and focusing mirrors, two reflective gratings, and a linear detector. The structural parameters were calculated using geometric configuration, dispersion, and aberrational theory, and conditions for first-order correction of keystone distortion with divergent grating illumination were derived. Based on this method, we simulated a spectrometer with a 16-channel linear array photomultiplier tube, resulting in uniformly distributed single-branch lines on each detector channel. The resolution reached 0.225 nm per channel, and the keystone distortion was less than 0.7%. The spectrometer avoids the interference of elastic signals by not detecting them, enabling the extraction of atmospheric temperature profiles via separated single-branch lines with high precision. Our design provides a promising solution to extract atmospheric temperature profiles for pure rotational Raman lidar.

Optimized Unilateral Magnetic Resonance Sensor with Constant Gradient and Its Applications in Composite Insulators.

In this study, an optimized unilateral magnetic resonance sensor with a three-magnet array is presented for assessing the aging of composite insulators in power grids. The sensor's optimization involved enhancing the static magnetic field strength and the homogeneity of the RF field while maintaining a constant gradient in the direction of the vertical sensor surface and maximizing homogeneity in the horizontal direction. The center layer of the target area was positioned 4 mm from the coil's upper surface, resulting in a magnetic field strength of 139.74 mT at the center point of the area, with a gradient of 2.318 T/m and a corresponding hydrogen atomic nuclear magnetic resonance frequency of 5.95 MHz. The magnetic field uniformity over a 10 mm × 10 mm range on the plane was 0.75%. The sensor measured 120 mm × 130.5 mm × 76 mm and weighed 7.5 kg. Employing the optimized sensor, magnetic resonance assessment experiments were conducted on composite insulator samples utilizing the CPMG (Carr-Purcell-Meiboom-Gill) pulse sequence. The T2 distribution provided visualizations of the T2 decay in insulator samples with different degrees of aging.

Biofilter-constructed wetland-trophic pond system: A new strategy for effective sewage treatment and agricultural irrigation in rural area.

Artificial ecosystems with high biological complexity are generally considered to be efficient in metabolizing substances and resistant to temperature shock. In this study, a novel near-natural system (BCT system), which consisted of simple biofilter, constructed wetland and trophic biology pond, was conducted to treat rural sewage in situ for irrigation into farmland. Water quality related to carbon and nutrients and microbial community were analyzed along the system to reveal the effect of each unit. The annual average removals of BCT system for TN, NH4+-N, TP and COD could reach 46.53%, 52.18%, 41.48%, and 53.21%, respectively. There was no significant decrease for removal efficiencies from high temperature period (HTP, ≥15 °C) to low temperature period (LTP, <15 °C). In LTP, the trophic pond (TRP) removed 34.85% of TN, 33.93% of NH4+-N, 13.71% of TP and 18.77% of COD, while the removal efficiencies of constructed wetland fluctuated greatly. The TRP facilitated the BCT system to maintain the removal capability during low temperature period. The relative abundance of denitrification functional genes in TRP increased nearly tenfold from HTP to LTP. The effluent quality from the system can meet the agricultural irrigation standards, demonstrating the effect of BCT system on sewage treatment and agricultural irrigation in rural area.

Design of Multicomponent Peptide Fibrils with Ordered and Programmable Compositional Patterns.

Advanced applications of biomacromolecular assemblies require a stringent degree of control over molecular arrangement, which is a challenge to current synthetic methods. Here we used a neighbor-controlled patterning strategy to build multicomponent peptide fibrils with an unprecedented capacity to manipulate local composition and peptide positions. Eight peptides were designed to have regulable nearest neighbors upon co-assembly, which, by simulation, afforded 412 different patterns within fibrils, with varied compositions and/or peptide positions. The fibrils with six prescribed patterns were experimentally constructed with high accuracy. The controlled patterning also applies to functionalities appended to the peptides, as exemplified by arranging carbohydrate ligands at nanoscale precision for protein recognition. This study offers a route to molecular editing of inner structures of peptide assemblies, prefiguring the uniqueness and richness of patterning-based material design.

Smoothed accumulated spectra based wDSWF method for real-time wind vector estimation of pulsed coherent Doppler lidar.

Wind vector estimation method with high accuracy in the low signal-to-noise ratio region improves the performance of pulsed coherent Doppler lidar. The key to improving accuracy is to process the incorrect radial wind estimates or the distorted power spectra better. The smoothed accumulated spectra based weighted sine wave fitting method proposed here minimizes the effects of bad radial wind estimates by considering both signal intensity and wind spatial continuity. Leveraging spatial continuity from smoothed accumulated spectra, the weight coefficients and real-time wind vector profiles can be quickly determined with non-looped operations. Simulations and field experiments showed that the proposed method provides comparable or even slightly better quality and more available wind vector estimates than the filtered sine wave fitting method.

Cuticular protein genes involve heat acclimation of insect larvae under global warming.

Cuticular proteins (CPs) play important roles in insect growth and development. However, it is unknown whether CPs are related to heat tolerance. Cnaphalocrocis medinalis, a serious pest of rice, occurs in summer and exhibits strong adaptability to high temperature, but the underlying mechanism is unclear. Here, the role of CP genes in heat acclimation was studied. Heat tolerance of the heat-acclimated larvae was significantly stronger than the unacclimated larvae. The cuticular protein content in the heat-acclimated larvae was higher than that of the unacclimated larvae. 191 presumed CP genes of C. medinalis (CmCPs) were identified. Expression patterns of 14 CmCPs were different between the heat acclimated (S39) and unacclimated (S27) larvae under heat stress. CmCPs were specifically expressed in epidermis and the head except CmCPR20 mainly expressed in Malpighian tubules. CmCPR20 was upregulated in S39 while downregulated in S27, but CmTweedle1 and CmCPG1 were upregulated in S27 and downregulated in S39. RNAi CmTweedle1 or CmCPG1 remarkably decreased heat tolerance and cuticular protein content of the heat-acclimated larvae but not the unacclimated larvae. RNAi CmCPR20 decreased heat tolerance and cuticular protein content of the unacclimated larvae but not the heat-acclimated larvae. CmTweedle1 and CmCPG1 genes involve heat acclimation of C. medinalis.

The anti-tumor and renoprotection study of E-[c(RGDfK)2]/folic acid co-modified nanostructured lipid carrier loaded with doxorubicin hydrochloride/salvianolic acid A.

BACKGROUND: Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients' pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors. RESULTS: Nanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)2]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)2]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 µmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)2]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy. CONCLUSION: The E-[c(RGDfK)2]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy.