A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.

Fabrication of micron-sized boronate-decorated polyethyleneimine-grafted magnetic agarose beads for specific enrichment of ribonucleic acid.

Exploiting high-performance magnetic beads for specific enrichment of ribonucleic acid (RNA) has important significance in the biomedical research field. Herein, a simple strategy was proposed for fabricating boronate-decorated polyethyleneimine-grafted magnetic agarose beads (BPMAB), which can selectively isolate cis-diol-containing substances through boronate affinity. The size of the basic magnetic agarose beads was controlled through the emulsification of the water-in-oil emulsion with a high-speed shear machine, which enhanced the specific surface area of BPMAB. Subsequently, to modify more boronic acid ligands, branched PEI with excellent hydrophilicity and numerous reaction sites was grafted. 2,4-Difluoro-3-formylphenyl boronic acid (2,4-DFPBA) was covalently immobilized for selectively capturing cis-diol-containing substances under physiological condition (pH 7.4). The BPMAB with a diameter range from 1.86 µm to 11.60 µm possessed clearly spherical structure, and excellent magnetic responsiveness and suspension ability in aqueous solution. ß-Nicotinamide adenine dinucleotide (ß-NAD), a short-chain cis-diol carrying agent, was selected as a target molecule for evaluating the adsorption property of BPMAB and the maximum adsorption capacity of BPMAB for ß-NAD could reach 205.11 mg g-1. In addition, the BPMAB as adsorbent was used to selectively enrich RNA from mammalian cells. The maximum adsorption capacity of BPMAB for RNA was 140.50 mg g-1. Under optimized conditions, the BPMAB-based MSPE successfully enriched the high-quality total RNA with 28S to 18S ribosomal RNA ratios ranging from 2.06 to 2.16. According to the PCR analysis of GADPH gene, the extracted total RNA was successfully reverse transcribed into cDNA. Therefore, we believe that the BPMAB-based MSPE could be applicable for the specific enrichment of RNA from complex biological systems.

Environmental microbes alleviate antibiotic disturbance on plant endophytes in aquatic microcosms: Prospects for conferring fitness benefits.

Antibiotic pollution in water environment is an emerging threat to plant health. Developing efficient strategies to reassemble the antibiotic-tolerating endophytes will confer fitness benefits on host plants to alleviate antibiotic stress. Here, introducing environmental microbes was proved as a promising approach to reshape the antibiotic-tolerating plant endophytes under antibiotic stress in aquatic microcosms. The introduction of environmental microbes effectively relieved antibiotic-driven perturbation on plant endophytes, with reduced changes in bacterial diversity and differential bacterial taxa and functional genes. Moreover, introducing environmental microbes facilitated the enrichment of endophytic bacterial genera and functional genes related to drug metabolism, which possessed the potentials to degrade antibiotics. In addition, environmental microbes boosted antibiotic-reshaped endophytes to form more stable bacterial networks for stronger antibiotic tolerance. In consequence, the decreased growth inhibition of antibiotics on host plants and enhanced antibiotic removal from microcosms were achieved by introducing environmental microbes. These findings pursue environmental microbes as practical resources to assist plants in reshaping the stress-alleviating endophytes, potentially improving plant tolerance to water pollution.

Molecular Modification Strategies of Nitrilase for Its Potential Application in Agriculture.

Some feed source plants will produce secondary metabolites such as cyanogenic glycosides during metabolism, which will produce some poisonous nitrile compounds after hydrolysis and remain in plant tissues. The consumption of feed-source plants without proper treatment affect the health of the animals' bodies. Nitrilases can convert nitriles and have been used in industry as green biocatalysts. However, due to their bottleneck problems, their application in agriculture is still facing challenges. Acid-resistant nitrilase preparations, high-temperature resistance, antiprotease activity, strong activity, and strict reaction specificity urgently need to be developed. In this paper, the application potential of nitrilase in agriculture, especially in feed processing industry was explored, the source properties and catalytic mechanism of nitrilase were reviewed, and modification strategies for nitrilase application in agriculture were proposed to provide references for future research and application of nitrilase in agricultural and especially in the biological feed scene.

Non-classical Deactivation Mechanism in a Supported Intermetallic Catalyst for Propane Dehydrogenation.

Platinum-based supported intermetallic alloys (IMAs) demonstrate exceptional performance in catalytic propane dehydrogenation (PDH) primarily because of their remarkable resistance to coke formation. However, these IMAs still encounter a significant hurdle in the form of catalyst deactivation. Understanding the complex deactivation mechanism of supported IMAs, which goes beyond conventional coke deposition, requires meticulous microscopic structural elucidation. In this study, we unravel a nonclassical deactivation mechanism over a PtZn/γ-Al2O3 PDH catalyst, dictated by the PtZn to Pt3Zn nanophase transformation accompanied with dezincification. The physical origin lies in the metal support interaction (MSI) that enables strong chemical bonding between hydroxyl groups on the support and Zn sites on the PtZn phase to selectively remove Zn species followed by the reconstruction towards Pt3Zn phase. Building on these insights, we have devised a solution to circumvent the deactivation by passivating the MSI through surface modification of γ-Al2O3 support. By exchanging protons of hydroxyl groups with potassium ions (K) on the γ-Al2O3 support, such a strategy significantly minimizes the dezincification of PtZn IMA via diminished metal-support bonding, which dramatically reduces the deactivation rate from 0.2044 to 0.0587 h-1.

Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Towards Sustainable and Fire-Safe Thermosets Using Phosphorus-Containing Covalent Adaptable Networks.

Dynamic covalent chemistry is a promising strategy for developing recyclable thermosets and their carbon fiber reinforced composites, in line with the goal of green and sustainable development. However, a significant challenge lies in balancing the dynamic reversibility and the desired service performances, such as thermal, mechanical properties, and flame retardancy. It has hindered the broader application of dynamic materials beyond the initial proof of concept. This concept provides an overview of the current state of research on phosphorus-containing covalent adaptable networks (CANs), highlighting key designing and regulating principles for tailoring comprehensive properties including flame retardancy, mechanical and thermal properties, as well as dynamic behaviours such as malleability, reprocessability and degradability. Finally, new frontiers and opportunities in developing high-performance sustainable CANs-based thermosets and their carbon fiber composites for structural engineering applications are prospected.

Identification and transcriptome analysis of a photosynthesis deficient mutant of Populus davidiana Dode.

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.

Effect of different endometrial preparation methods on pregnancy outcome of FET in women with a normal menstrual cycle.

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease: A randomized double-blind placebo-controlled trial.

BACKGROUND: Patients with Parkinson's disease (PD) undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia (LID). Amantadine is the main drug recommended for the treatment of LID by current guidelines, but it is far from meeting clinical needs. Tianqi Pingchan Granule (TPG), a compound Chinese herbal medicine, has been developed to relieve symptom of LID. OBJECTIVE: This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a randomized double-blind placebo-controlled trial, conducted from January 2020 to August 2021 at 6 sites in Jiangsu, Zhejiang and Shanghai, China. One hundred PD patients with ≥ 0.5 h of LID were randomly assigned to either the TPG plus amantadine group (TPG group) or the placebo plus amantadine group (placebo group), and treated for a period of 12 weeks. To ensure unbiased results, all study participants, investigators and sponsors were unaware of group allocations. Additionally, the data analysts remained blinded until the analysis was finalized. MAIN OUTCOME MEASURES: The primary outcome was assessed using the Unified Dyskinesia Rating Scale (UDysRS) (Range 0-104). The key secondary end point was improvement of motor and non-motor symptoms. Safety analyses included all enrolled patients. RESULTS: One hundred patients were enrolled and randomized into the two treatment groups. The changes in UDysRS at week 12 were -11.02 for the TPG group and -4.19 for the placebo group (treatment difference -6.83 [-10.53 to -3.12]; P = 0.0004). Adverse events were reported for 2 of 50 patients (4.0%) in each of the groups. CONCLUSION: This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated, demonstrating the efficacy and safety of TPG for the treatment of LID in PD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04173832. PLEASE CITE THIS ARTICLE AS: Zhang Y, Zhu XB, Zhao Y, Cui GY, Li WT, Yuan CX, Huang JP, Wan Y, Wu N, Song L, Zhao JH, Liang Y, Xu CY, Liu MJ, Gao C, Chen XX, Liu ZG. Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease: A randomized double-blind placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

Rationally designed Ru catalysts supported on TiN for highly efficient and stable hydrogen evolution in alkaline conditions.

Electrocatalysis holds the key to enhancing the efficiency and cost-effectiveness of water splitting devices, thereby contributing to the advancement of hydrogen as a clean, sustainable energy carrier. This study focuses on the rational design of Ru nanoparticle catalysts supported on TiN (Ru NPs/TiN) for the hydrogen evolution reaction in alkaline conditions. The as designed catalysts exhibit a high mass activity of 20 A mg-1Ru at an overpotential of 63 mV and long-term stability, surpassing the present benchmarks for commercial electrolyzers. Structural analysis highlights the effective modification of the Ru nanoparticle properties by the TiN substrate, while density functional theory calculations indicate strong adhesion of Ru particles to TiN substrates and advantageous modulation of hydrogen adsorption energies via particle-support interactions. Finally, we assemble an anion exchange membrane electrolyzer using the Ru NPs/TiN as the hydrogen evolution reaction catalyst, which operates at 5 A cm-2 for more than 1000 h with negligible degradation, exceeding the performance requirements for commercial electrolyzers. Our findings contribute to the design of efficient catalysts for water splitting by exploiting particle-support interactions.

Bavachinin, a main compound of Psoraleae Fructus, facilitates GSDMD-mediated pyroptosis and causes hepatotoxicity in mice.

Psoraleae Fructus (PF, Psoralea corylifolia L.), a traditional medicine with a long history of application, is widely used clinically for the treatment of various diseases. However, the reports of PF-related adverse reactions, such as hepatotoxicity, phototoxic dermatitis, and allergy, are increasing year by year, with liver injury being the mostly common. Our previous studies have demonstrated that PF and its preparations can cause liver injury in lipopolysaccharide (LPS)-mediated susceptibility mouse model, but the mechanism of PF-related liver injury is unclear. In this study, we showed that PF and bavachinin, a major component of PF, can directly induce the expression of caspase-1 and interleukin-1ß (IL-1ß), indicating that PF and bavachinin can directly triggered the activation of inflammasome. Furthermore, pretreatment with NLR family pyrin domain-containing 3 (NLRP3), NLR family CARD domain containing 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome inhibitors, containing MCC950, ODN TTAGGG (ODN) and carnosol, all significantly reversed bavachinin-induced inflammasome activation. Mechanistically, bavachinin dose-dependently promote Gasdermin D (GSDMD) post-shear activation and then induce mitochondrial reactive oxygen species (mtROS) production and this effect is markedly inhibited by pretreatment with N-Acetylcysteine amide (NAC). In addition, combination treatment of LPS and bavachinin significantly induced liver injury in mice, but not LPS or bavachinin alone, and transcriptome analysis further validated these results. Thus, PF and bavachinin can induce the activation of inflammasome by promoting GSDMD cleavage and cause hepatotoxicity in mice. Therefore, PF, bavachinin, and PF-related preparations should be avoided in patients with inflammasome activation-associated diseases.

Six-compound combo remedy ameliorates corticosterone-induced depressive behaviors in mice via targeting HTR1A signaling.

Dysregulation of brain innate immunity involving microglia is implicated in the pathology of neurological disorders including depression. Depression is a prominent medical challenge to global public health systems. Synthetic antidepressant drugs are limited by severe side-effects. The present study aimed to identify the active compounds from the well-documented herbal medicine formula Banxia-Houpo decoction (BHD) and discover the underlying mechanisms for tuning microglia. We initially employed LC-MS profiling and network pharmacology analysis to predict the active compound-target interaction networks. We subsequently validated the potential active compounds and targets in a mouse model of corticosterone (CORT)-induced depression and post-synaptic microglia BV2 cells. As results, 64 compounds were identified in the ethanolic BHD extract and predicted to target 25 depression-related genes. Interestingly, the serotonergic synapse pathway received the highest enrichment score while 5-hydroxytryptamine receptor 1A (HTR1A) was targeted by six compounds (i.e., baicalein, luteolin, N-nornuciferine, roemerine, scutellarin, 6-shogaol). In parallel assays, a six-compound combo (SCC) and BHD markedly ameliorated the depressive-like behaviors in CORT-lesioned mice and well protected highly differentiated (HD) PC12 cells against CORT challenge. Moreover, SCC and BHD effectively induced HTR1A expression in mice and post-synaptic microglia BV2 cells. HTR1A antagonist WAY-100635 at 1mg/kg/d via intraperitoneal injection attenuated the effects of SCC and BHD on the depressive behaviors in mice. These results suggest that SCC might be a potential remedy against depression and other neurological disorders via targeting HTR1A in microglia.

PDX1+ cell budding morphogenesis in a stem cell-derived islet spheroid system.

Remarkable advances in protocol development have been achieved to manufacture insulin-secreting islets from human pluripotent stem cells (hPSCs). Distinct from current approaches, we devised a tunable strategy to generate islet spheroids enriched for major islet cell types by incorporating PDX1+ cell budding morphogenesis into staged differentiation. In this process that appears to mimic normal islet morphogenesis, the differentiating islet spheroids organize with endocrine cells that are intermingled or arranged in a core-mantle architecture, accompanied with functional heterogeneity. Through in vitro modelling of human pancreas development, we illustrate the importance of PDX1 and the requirement for EphB3/4 signaling in eliciting cell budding morphogenesis. Using this new approach, we model Mitchell-Riley syndrome with RFX6 knockout hPSCs illustrating unexpected morphogenesis defects in the differentiation towards islet cells. The tunable differentiation system and stem cell-derived islet models described in this work may facilitate addressing fundamental questions in islet biology and probing human pancreas diseases.

Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.

Regulated cell death (RCD) is a controlled form of cell death orchestrated by one or more cascading signaling pathways, making it amenable to pharmacological intervention. RCD subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis, facilitating development, and modulating immunity. Accumulating evidence has recently revealed that RCD evasion is frequently the primary cause of tumor survival. Several non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse, comparable to apoptosis. Moreover, they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic drugs. With an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines, a growing number of small-molecule compounds targeting single or multiple pathways have been discovered, providing novel strategies for current cancer therapy. In this review, we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines, mainly including autophagy-dependent cell death, ferroptosis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, alkaliptosis, oxeiptosis, parthanatos, mitochondrial permeability transition (MPT)-driven necrosis, entotic cell death, NETotic cell death, lysosome-dependent cell death, and immunogenic cell death (ICD). Furthermore, we focused on discussing the pharmacological regulatory mechanisms of related small-molecule compounds. In brief, these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines, ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.

The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins.

Vesicle trafficking is a fundamental process that allows for the sorting and transport of specific proteins (i.e., "cargoes") to different compartments of eukaryotic cells. Cargo recognition primarily occurs through coats and the associated proteins at the donor membrane. However, it remains unclear whether cargoes can also be selected at other stages of vesicle trafficking to further enhance the fidelity of the process. The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complex to facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EM structure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizes a subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complex assembly and its binding to SAC-containing proteins are indispensable for the trafficking of SAC-containing proteins and proper neuronal development in zebrafish. Our studies thus uncover that cargo proteins could be recognized in a sequence-specific manner downstream of a protein coat.

A non-invasive osteopontin-targeted phase changeable fluorescent nanoprobe for molecular imaging of myocardial fibrosis.

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.