Generation of rat forebrain tissues in mice.

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study.

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.

A self-assembly active nanomodulator based on berberine for photothermal immunotherapy of breast cancer via dual regulation of immune suppression.

Breast cancer (BC) remains a significant global health concern, especially affecting women, necessitating the development of effective treatment strategies. Photothermal immunotherapy has holds promise for addressing BC by eradicating tumors, preventing metastasis, and reducing recurrence rates. However, the dynamic amplification of indoleamine 2,3-dioxygenase 1 (IDO-1) and programmed cell death-ligand 1 (PD-L1) triggered by photothermal therapy (PTT) poses presents a significant barrier to immune cell infiltration, thus promoting immune evasion. To enhance overall efficiency, a hyaluronic acid (HA)-coated berberine (BBR)-indocyanine green self-assembly active nano modulator (HBI NDs) was successfully developed. This nano modulator aims to reverse immune resistance and further contribute to the synergistic anti-tumor effects. The prepared HBI NDs demonstrated a uniform spherical morphology, high drug loading, and favorable optical properties. The results based on in vitro cell experiments and tumor animal models confirmed that HBI NDs selectively accumulated in tumor tissues, downregulated PD-L1 and IDO-1 protein expression, and induced elevated cell apoptosis. Consequently, these effects result in efficient immune infiltration and positive anti-tumor outcomes. In conclusion, the HBI NDs nanodrug exhibits considerable potential as a novel agent for enhancing anticancer efficacy and promoting immune infiltration.

Enhanced C-To-T and A-To-G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED.

Mitochondrial base editing with DddA-derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C-to-T targeting scope by fusing DddA11 variant with different cytosine deaminases with single-strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation-induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5'-GC-3' sequence, but also elevates editing efficiency at 5'-TC-3', 5'-CC-3', and 5'-GC-3' targets by up to 25-, 10-, and 6-fold, respectively. Furthermore, the A-to-G editing efficiency is significantly improved by fusing the evolved DddA6 variant with TALE-linked deoxyadenosine deaminase (TALED). Notably, the authors introduce the reported high-fidelity mutations in DddA and add nuclear export signal (NES) sequences in DdCBE and TALED to reduce off-target editing in the nuclear and mitochondrial genome while improving on-target editing efficiency in mitochondrial DNA (mtDNA). Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.

Physicochemical Index Analyses of the Egg White in Blue-Shelled Eggs and Commercial Brown-Shelled Eggs during Storage.

To compare the physical and chemical changes in egg whites during storage, assisting in the evaluation of differences in egg freshness between various chicken breeds, we chose 240 blue-shelled eggs (Blue group) and 240 commercial brown-shelled eggs (Brown group) that 28-week-old hens had laid. In this study, all eggs were stored at 25 °C. The egg weight, egg components' weight and proportion, Haugh Unit value and the contents of S-ovalbumin, ovomucin and lysozyme in the thick albumen (KA) and thin albumen (NA) were measured at eight time points every 3 days until the 21st day of storage. The eggshell, yolk and KA proportions in the Brown group were significantly lower, whereas the NA proportion was significantly higher than that in the Blue group (p < 0.001). The Haugh Unit value and S-ovalbumin in the Brown group were significantly higher, whereas KA ovomucin and NA lysozyme were significantly lower than those in the Blue group (p < 0.001). There existed significant negative correlations between the KA and NA, irrespective of weight or proportion. The Haugh Unit value was significantly positively correlated with lysozyme and ovomucin, but significantly negatively correlated with S-ovalbumin. During storage, the KA weight (proportion), Haugh Unit value, lysozyme and ovomucin decreased, whereas the NA weight (proportion) and S-ovalbumin increased. At each time point, the NA lysozyme in the Brown group was lower than that in the Blue group (p < 0.05). After storage for 6 days, the KA ovomucin in the Brown group began to be lower than that in the Blue group (p < 0.05). The study showed that the weight (proportion) differences in egg components between blue-shelled eggs and commercial brown-shelled eggs are mainly due to the NA. The Haugh Unit value and albumin protein indexes of blue-shelled eggs were better than those of brown-shelled eggs, and showed mild changes during storage, indicating the better storage performance of blue-shelled eggs.

An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.

BACKGROUND: Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa. METHODS: We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event. RESULTS: The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination. CONCLUSIONS: Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.

Bivariate copula regression models for semi-competing risks.

Time-to-event semi-competing risk endpoints may be correlated when both events occur on the same individual. These events and the association between them may also be influenced by individual characteristics. In this article, we propose copula survival models to estimate hazard ratios of covariates on the non-terminal and terminal events, along with the effects of covariates on the association between the two events. We use the Normal, Clayton, Frank and Gumbel copulas to provide a variety of association structures between the non-terminal and terminal events. We apply the proposed methods to model semi-competing risks of graft failure and death for kidney transplant patients. We find that copula survival models perform better than the Cox proportional hazards model when estimating the non-terminal event hazard ratio of covariates. We also find that the inclusion of covariates in the association parameter of the copula models improves the estimation of the hazard ratios.

Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase.

Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine (C) or adenine (A), but no method for guanine (G) or thymine (T) editing is available at present. Here we developed a deaminase-free glycosylase-based guanine base editor (gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 fold. Furthermore, this gGBE exhibited high base editing efficiency (up to 81.2%) and high G-to-T or G-to-C (i.e. G-to-Y) conversion ratio (up to 0.95) in both cultured human cells and mouse embryos. Thus, we have provided a proof-of-concept of a new base editing approach by endowing the engineered DNA glycosylase the capability to selectively excise a new type of substrate.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

The pigments in eggshell with different colour and the pigment regulatory gene expression in corresponding chicken's shell gland.

Eggshell colour is the unique appearance and economically valuable trait of eggs, whereas the colour is often short of uniformity, especially in the blue-shelled breeds, hence, their pigment differences and molecular mechanism need clarity. To investigate the relationship between the pigment content of eggshells and related gene expression in the eggshell glands of chickens, four subtypes of blue-shelled eggs ('Olive', 'Green', 'Blue', and 'Light') from the same blue-eggshell chicken line were selected; Hy-Line 'White' and 'Brown'-shelled eggs were used as control groups. The L*, a*, b* values, and protoporphyrin-IX and biliverdin contents in each group of eggshells were measured. In addition, the shell glands of the corresponding hens were collected to detect SLCO1B3 genotype and mRNA expression, and ABCG2 and HMOX1 transcription and protein expression. Eggshell colour L* values were negatively correlated with protoporphyrin-IX, b* values were positively correlated with total pigment content (P < 0.001), and a* values were positively correlated with protoporphyrin-IX (P < 0.001) but negatively with biliverdin. Moreover, all four blue-eggshell subtypes were SLCO1B3 homozygous, with SLCO1B3 mRNA expression in shell glands being significantly higher than in the White and Brown groups. ABCG2 and HMOX1 mRNA expression were highest in the Brown and Green groups, respectively (P < 0.05), and were positively correlated with protoporphyrin-IX (P < 0.001) and biliverdin contents in eggshells, respectively. Western blot and immunohistochemical results demonstrated that the Brown group had the highest ABCG2 expression (P < 0.05), followed by the Green and Olive groups. HMOX1 protein expression was higher in the Olive and Green groups (P < 0.05), and lowest in the White group. This study suggests that ABCG2 and HMOX1 have important regulatory roles in the production and transport of protoporphyrin-IX and biliverdin in blue-shelled chicken eggs, respectively.

Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing.

The type V-F CRISPR-Cas12f system is a strong candidate for therapeutic applications due to the compact size of the Cas12f proteins. In this work, we identify six uncharacterized Cas12f1 proteins with nuclease activity in mammalian cells from assembled bacterial genomes. Among them, OsCas12f1 (433 aa) from Oscillibacter sp. and RhCas12f1 (415 aa) from Ruminiclostridium herbifermentans, which respectively target 5' T-rich Protospacer Adjacent Motifs (PAMs) and 5' C-rich PAMs, show the highest editing activity. Through protein and sgRNA engineering, we generate enhanced OsCas12f1 (enOsCas12f1) and enRhCas12f1 variants, with 5'-TTN and 5'-CCD (D = not C) PAMs respectively, exhibiting much higher editing efficiency and broader PAMs, compared with the engineered variant Un1Cas12f1 (Un1Cas12f1_ge4.1). Furthermore, by fusing the destabilized domain with enOsCas12f1, we generate inducible-enOsCas12f1 and demonstate its activity in vivo by single adeno-associated virus delivery. Finally, dead enOsCas12f1-based epigenetic editing and gene activation can also be achieved in mammalian cells. This study thus provides compact gene editing tools for basic research with remarkable promise for therapeutic applications.

Dexmedetomidine alleviates oxidative stress and mitochondrial dysfunction in diabetic peripheral neuropathy via the microRNA-34a/SIRT2/S1PR1 axis.

OBJECTIVE: Dexmedetomidine (Dex) is a highly selective α2-adrenoceptor agonist with sedative, analgesic, sympatholytic, and hemodynamic-stabilizing properties, which plays a neuroprotective role in diabetic peripheral neuropathy (DPN) and diabetes-induced nerve damage. However, the related molecular mechanisms are not fully understood. Therefore, our study explored the mechanism of Dex in DPN using rat and RSC96 cell models. METHODS: Sciatic nerve sections were observed under an optical microscope and the ultrastructure of the sciatic nerves was observed under a transmission electron microscope. Oxidative stress was assessed by detecting MDA, SOD, GSH-Px, and ROS levels. The motor nerve conduction velocity (MNCV), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) of rats were measured. Cell viability, apoptosis, and the changes in the expression of related genes and proteins were examined. Furthermore, the relationship between microRNA (miR)-34a and SIRT2 or SIRT2 and S1PR1 was analyzed. RESULTS: Dex reversed DPN-induced decreases in MNCV, MWT, and TWL. Dex alleviated oxidative stress, mitochondrial damage, and apoptosis in both the rat and RSC96 cell models of DPN. Mechanistically, miR-34a negatively targeted SIRT2, and SIRT2 inhibited S1PR1 transcription. The overexpression of miR-34a or S1PR1 or the inhibition of SIRT2 counteracted the neuroprotective effects of Dex in DPN in vivo and in vitro. CONCLUSION: Dex alleviates oxidative stress and mitochondrial dysfunction associated with DPN by downregulating miR-34a to regulate the SIRT2/S1PR1 axis.

Ultrathin Solid Polymer Electrolyte Design for High-Performance Li Metal Batteries: A Perspective of Synthetic Chemistry.

Li metal batteries (LMBs) have attracted widespread attention in recent years because of their high energy densities. But traditional LMBs using liquid electrolyte have potential safety hazards, such as: leakage and flammability. Replacing liquid electrolyte with solid polymer electrolyte (SPE) can not only significantly improve the safety, but also improve the energy density of LMBs. However, till now, there is only limited success in improving the various physical and chemical properties of SPE, especially in thickness, posing great obstacles to further promoting its fundamental and applied studies. In this review, the authors mainly focus on evaluating the merits of ultrathin SPE and summarizing its existing challenges as well as fundamental requirements for designing and manufacturing advanced ultrathin SPE in the future. Meanwhile, the authors outline existing cases related to this field as much as possible and summarize them from the perspective of synthetic chemistry, hoping to provide a comprehensive understanding and serve as a strategic guidance for designing and fabricating high-performance ultrathin SPE. Challenges and opportunities regarding this burgeoning field are also critically evaluated at the end of this review.

Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors.

Photothermal therapy (PTT) has brought hope for cancer treatments, with hyperthermia-induced immunogenic cell death (ICD), which is a critical part of therapeutically induced antitumor immune responses. Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation, therefore demonstrating urgent requirements for ICD amplifier. Herein, a sub-10 nm supramolecular nanoassembly was formed by co-assembly of clinically approved aluminum adjuvant and commonly used indocyanine green (ICG) under the assistance of lignosulfonate (LS, a green and sustainable multifunctional lignin derivative) for localized photothermal-immunotherapy of breast cancer. The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD, efficiently eliciting solid immune responses through dendritic cells (DCs) activation and cytotoxic T-cell responses initiation for tumor killing. Moreover, anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity. The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy, which shows promise for delivering other therapeutics in biomedical applications.

Synergistic Effects of Diatoms on Intumescent Flame Retardant High Impact Polystyrene System.

In this work, aiming to improve the flame retardancy performance of high impact polystyrene (HIPS), HIPS compounds were synthesized with the addition of intumescent flame retardant (IFR: mass ratio of APP and PER was 3:1) and diatoms into HIPS matrix by melt blending method. It was found the IFR/diatoms system exhibited high flame retardant efficiency and catalytic carbonization effect to HIPS matrix in the burning process. The LOI value of HIPS-2 compound with the addition of 28 wt% IFR and 2 wt% diatoms was increased to 29.0% and passed V-0 rating. The value of PHRR for HIPS-2 compound is about 460.58 kW/m2 compared with 937.22 kW/m2 of pure HIPS and the value of THR for HIPS-2 compound is about 32.9 MJ/m2 compared with 62.7 MJ/m2 of pure HIPS, suggesting that the addition of IFR/diatoms system can decrease the values of PHRR and THR, which shows the synergistic effect between IFR and diatoms on reducing heat release. The 21.9% reduction in Av-EHC and 41.4% reduction in TSP seen on introducing an IFR/diatoms system indicates effective smoke suppression, which potentially would significantly reduce the death rate in real fire accidents. The TG-IR results indicated that the IFR/diatoms flame retardant system functioned in the gas phase to suppress the flame. The SEM images showed the char residue produced was more compact and continuous, which suggests that the IFR/diatoms flame retardant system exhibits barrier and catalytic effects to block heat transferring and promote char forming. The tensile strength and impact strength of HIPS-2 compound were 22.95 MPa and 2.63 KJ/m2, respectively. The tensile strength and impact strength were increased by 34.13% and 19.55% compared with that of pure HIPS.

The Corticosterone-Glucocorticoid Receptor-AP1/CREB Axis Inhibits the Luteinizing Hormone Receptor Expression in Mouse Granulosa Cells.

Under stress conditions, luteinizing hormone (LH)-mediated ovulation is inhibited, resulting in insufficient oocyte production and excretion during follicular development. When the body is stressed, a large amount of corticosterone (CORT) is generated, which will lead to a disorder of the body's endocrine system and damage to the body. Our previous work showed that CORT can block follicular development in mice. Since LH acts through binding with the luteinizing hormone receptor (Lhcgr), the present study aimed to investigate whether and how corticosterone (CORT) influences Lhcgr expression in mouse ovarian granulosa cells (GCs). For this purpose, three-week-old ICR female mice were injected intraperitoneally with pregnant mare serum gonadotropin (PMSG). In addition, the treatment group was injected with CORT (1 mg/mouse) at intervals of 8 h and the control group was injected with the same volume of methyl sulfoxide (DMSO). GCs were collected at 24 h, 48 h, and 55 h after PMSG injection. For in vitro experiments, the mouse GCs obtained from healthy follicles were treated with CORT alone, or together with inhibitors against the glucocorticoid receptor (Nr3c1). The results showed that the CORT caused a downregulation of Lhcgr expression in GCs, which was accompanied by impaired cell viability. Moreover, the effect of the CORT was mediated by binding to its receptor (Nr3c1) in GCs. Further investigation revealed that Nr3c1 might regulate the transcription of Lhcgr through inhibiting the expression of Lhcgr transcription factors, including AP1 and Creb. Taken together, our findings suggested a possible mechanism of CORT-induced anovulation involving the inhibition of Lhcgr expression in GCs by the CORT-Nr3c1-AP1/Creb axis.

The Influence of Metal Lithium and Alkyl Chain in the Nucleating Agent Lauroyloxy-Substituted Aryl Aluminum Phosphate on the Crystallization and Optical Properties for iPP.

In this work, a kind of aryl phosphate salt nucleating agent (APAl-12C) was synthesized, which was replaced in the hydroxyl group on the aluminum hydroxy bis [2,2'-methylene-bis(4,6-di-tert-butylphenyl) phosphate] (APAl-OH) by lauroyloxy, which could improve the dispersion between the nucleating agent and the iPP matrix and reduce the migration potential of the nucleating agent in the iPP matrix by increasing the molecular weight. The structure of the nucleating agent APAl-12C was analyzed by fourier infrared spectroscopy (FT-IR ) and 1H NMR. The differential scanning calorimeter (DSC) results indicated that the addition of APAl-OH or APAl-12C alone was inferior to the commercial nucleating agent NA-21 (compounds of APAl-OH and Lithium laurate) in terms of the crystallization behavior, which may be due to the importance of metal Li in the crystallization property. Thus, the iPP/A12C-Li composites were prepared with APAl-12C, lithium laurate (lilaurate) and the iPP matrix. The crystallization behavior, morphology, optical and mechanical properties for the iPP/A12C-Li composites were systematically studied and compared with that of the iPP/NA-21 composite. Among the iPP/A12C-Li composites with the addition of 0.5 wt%, APAl-12C/Lilaurate had the fastest crystallization rate and reduced the haze value of the neat iPP from 36.03% to 9.89% without changing the clarity, which was better than that of the iPP/NA-21 composite. This was due to the weakening of the polarity of the APAl-12C after lauroyloxy substitution and better dispersion in the iPP matrix, resulting in a significant improvement in the optical properties.

Cooperative coordination-mediated multi-component self-assembly of "all-in-one" nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer.

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO4 3-) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an "all-in-one" theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.