Neural habituation during acute stress signals a blunted endocrine response and poor resilience.

BACKGROUND: A blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated. METHODS: Seventy-seven participants (17-22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17-22 years old, 24 women). RESULTS: Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response. CONCLUSIONS: This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.

Role of hippocampus and orbitofrontal cortex in the association of interdependent self-construal with an acute stress response.

Empirical evidence indicates that high interdependent self-construal (InterSC) is correlated with exaggerated acute stress responses; however, the underlying neural correlates remain unclear. Considering the regulatory effect of the prefrontal cortex and limbic system on the acute stress response, the primary aim of this study was to investigate the role of the orbitofrontal cortex (OFC) and hippocampus (HIP) in the relationship between InterSC and acute stress responses. Forty-eight healthy college students underwent a modified version of the Montreal imaging stress task (MIST), while brain activity was recorded using functional magnetic resonance imaging (fMRI). Participants' saliva samples and subjective stress feelings were collected before, during, and after the MIST. Additionally, participants' self-construal was measured using questionnaires. Results revealed that InterSC was positively correlated with the activation of OFC, which, in turn, was associated with higher subjective stress feelings. A higher InterSC was also significantly associated with an enhanced salivary cortisol response in those with lower HIP activity. Furthermore, the HIP moderated the indirect effect of InterSC on subjective stress feelings by moderating the effect of InterSC on neural activity in the OFC. This indicated the mediation of the OFC was stronger in those with higher neural activity in the HIP than in those with lower activity in the HIP. In summary, the current study proposed an important role of the OFC-HIP regions in the relationship between InterSC and acute stress responses, making contribution to broadening the field of personality and stress and deepening our understanding of individual differences in acute stress responses.

Hair Cortisone Predicts Lower Stress-induced Salivary Cortisol Response: Resting-state Functional Connectivity Between Salience and Limbic Networks.

Previous studies revealed that high long-term hypothalamic-pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain's resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. Saliva samples were collected to assess the levels of acute stress salivary cortisol. Hair samples were also collected, and the corticosteroid concentration extracted from these samples were used as a biomarker of long-term HPA axis activity. High hair cortisone (HairE) levels predicted lower acute stress cortisol response. Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.

Identification of specific and shared epitopes at the extreme N-terminal VP1 of Coxsackievirus A4, A2 and A5 by monoclonal antibodies.

Hand, foot and mouth disease (HFMD) is caused by a variety of serotypes in species A of the Enterovirus genus, including recently re-emerged Coxsackievirus A2 (CV-A2), CV-A4 and CV-A5. For development of diagnostic reagents, for surveillance, and the development of multivalent vaccines against HFMD, the antigenicity of HFMD-associated enteroviruses warrants investigation. The purified virions of CV-A4 were inoculated into Balb/c mice and hybridomas were obtained secreting monoclonal antibodies (mAbs) directed against CV-A4 and cross-reacting with other closely related species A enteroviruses. The mAbs were characterized by ELISA, Western blotting and in vitro neutralizing assays. The majority of mAbs was non-neutralizing, with only 2% of the mAbs neutralizing CV-A4 specifically. Most of mAbs bound to linear VP1 epitopes of CV-A4. Interestingly, four types of mAbs were obtained which bound specifically to CV-A4 or were broadly to CV-A4/-A2, CV-A4/-A5 and CV-A4/-A2/-A5, respectively. Mapping with overlapping or single-amino-acid mutant peptides revealed that the four types of mAbs all bound to the first 15 amino acids at the N-terminus of the VP1. This region of picornaviruses is functionally important as it is involved in uncoating and releasing of viral RNA into the cytosol. The binding footprints of four type mAbs are composed of conserved and variable residues and are different from each other. The newly discovered broadly cross-reactive mAbs reflect the high homology of CV-A4/ CV-A2/CV-A5. The results also demonstrate that it is possible and beneficial to develop the diagnostic reagents to detect rapidly the main pathogens of enteroviruses associated with HFMD cause by CV-A4/CV-A2/CV-A5.

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways.

Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), a natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little is known about the effect of MA on OA. We aim to examine the role of MA on OA and to identify the potential mechanisms through which it protects articular cartilage. In vitro, MA improved inflammatory response, anabolism, and catabolism in IL-1ß-induced OA chondrocytes. The chondroprotective effects of MA were attributed to suppressing the MAPK, NF-κB, and PI3K-AKT-mTOR signaling pathways, as well as promoting the autophagy process. In vivo, intra-articular injection of MA reduced the cartilage destruction and reversed the change of anabolic and catabolic-related proteins in destabilized medial meniscus (DMM)-induced OA models. Thus, the study indicates that MA exhibits a chondroprotective effect and might be a promising agent for OA treatment.

AZD6738 decreases intraocular pressure and inhibits fibrotic response in trabecular meshwork through CHK1/P53 pathway.

In this study, we report that AZD6738 (Ceralasertib), a novel potent ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, can decrease intraocular pressure (IOP) and inhibits fibrotic response in the trabecular meshwork (TM). We established mice TGF-ß2-induced high IOP model and revealed that AZD6738 could effectively decrease IOP in the mice model and reduce TGF-ß2-induced hyperplasia, collagen production, fibrosis, and extracellular matrix (ECM) remodeling in the TM by downregulating checkpoint kinase 1 (CHK1) level. Further, we demonstrated that AZD6738 reduces cell viability and migration, and inhibit the expression of fibrosis-related factors including fibronectin (FN), α-smooth muscle actin (α-SMA), laminin subunit beta 1 (LAMB1), matrix metallopeptidase (MMP) family including MMP2 and MMP9, collagen Ⅰ (COL1), and collagen Ⅳ (COL4), reduce gap junctions, altered cytoskeleton and nitric oxide production in TGF-ß1-induced human trabecular meshwork cells (HTMCs) through the CHK1/P53 pathway, which were affected aqueous humor (AH) production and outflow pathway. In addition, we preliminarily verified the safety of the AZD6738 in topical ophthalmic use. Hence, our results demonstrate that AZD6738 may become a potential therapeutic option for anti-glaucoma.

Reward sensitivity modulates the brain reward pathway in stress resilience via the inherent neuroendocrine system.

In the previous 10 years, researchers have suggested a critical role for the brain reward system in stress resilience. However, no study has provided an empirical link between activity in the mesostriatal reward regions during stress and the recovery of cortisol stress response. Moreover, although reward sensitivity as a trait has been demonstrated to promote stress resilience, it remains unclear whether it modulates the brain reward system in stress resilience and how this effect is achieved by the inherent neuroendocrine system. To investigate these uncertainties, 70 young adults were recruited to participate in a ScanSTRESS task, and their brain imaging data and saliva samples (for cortisol assay) were collected during the task. In addition, we assessed reward sensitivity, cortisol awakening response, and intrinsic functional connectivity of the brain in all the participants. We found that left putamen activation during stress exposure positively predicted cortisol recovery. In addition, reward sensitivity was positively linked with activation of the left putamen, and this relationship was serially mediated by the cortisol awakening response and right hippocampus-left inferior frontal gyrus intrinsic connectivity. These findings suggest that reward sensitivity modulates reward pathways in stress resilience through the interplay of the diurnal stress response system and network of the hippocampus-prefrontal circuitry. Summarily, the current study built a model to highlight the dynamic and multifaceted interaction between pertinent allostatic factors in the reward-resilience pathway and uncovered new insight into the resilience function of the mesostriatal reward system during stress.

Evaluation of reconstructed auricles by convolutional neural networks.

The difficulty in determining which structures are crucial to ensure a natural-looking ear has been plaguing surgeons for many years. This preliminary study explores the feasibility of training convolutional neural network (CNN) models to evaluate a reconstructed auricle as accurate as a human would. By visualizing the attention of trained models, the criteria for the design of a natural-looking auricle can be established. A total of 400 pictures were evaluated by 20 volunteers, and 20 labeled datasets were generated, which were then used to train ResNet models that had been pre-trained on ImageNet. The saliency maps and occlusion maps of each trained model were calculated to capture the attention of models. The average accuracy of the 20 models was 0.8245 ± 0.0356 (>0.80), and the evaluation results of the trained model and the medical student showed a significant correlation (P < 0.05). For the attention visualization of auricles labeled as normal, distribution of the highlighted portions corresponded to a linear contour of the helix, the inferior crura of the antihelix, and the contour of the concha. A CNN can provide an evaluation of a reconstructed auricle in a manner similar to that of a medical student. Saliency maps generated by the CNN demonstrate the subjective view, which was consistent with professional opinion.

Emergence of a novel recombinant of CV-A5 in HFMD epidemics in Xiangyang, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is caused by a variety of enterovirus serotypes and the etiological spectrum worldwide has changed since a large scale of outbreaks occurred in 1997. METHODS: A large number of clinical specimens of HFMD patients were collected in Xiangyang and genotyping was performed by qRT-PCR, conventional PCR amplification and sequencing. Among the 146 CV-A5 detected cases, the complete genome sequences of representative strains were determined for genotyping and for recombination analysis. RESULTS: It was found that CV-A5 was one of the six major serotypes that caused the epidemic from October 2016 to December 2017. Phylogenetic analyses based on the VP1 sequences showed that these CV-A5 belonged to the genotype D which dominantly circulated in China. Recombination occurred between the CV-A5 and CV-A2 strains with a breakpoint in the 2A region at the nucleotide 3791. CONCLUSIONS: The result may explain the emergence of CV-A5 as one of the major pathogens of HFMD. A multivalent vaccine against HFMD is urgently needed to control the disease and to prevent emerging and spreading of new recombinants.

Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy.

Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.

Efficacy of a coxsackievirus A6 vaccine candidate in an actively immunized mouse model.

Coxsackievirus A6 (CV-A6) has been emerging as a major pathogen of hand, foot and mouth disease (HFMD). Study on the pathogenesis of CV-A6 infection and development of vaccines is hindered by a lack of appropriate animal models. Here, we report an actively immunized-challenged mouse model to evaluate the efficacy of a Vero-cell-based, inactivated CV-A6 vaccine candidate. The neonatal Kunming mice were inoculated with a purified, formaldehyde-inactivated CV-A6 vaccine on days 3 and 9, followed by challenging on day 14 with a naturally selected virulent strain at a lethal dose. Within 14 days postchallenge, all mice in the immunized groups survived, while 100% of the Alum-only inoculated mice died. Neutralizing antibodies (NtAbs) were detected in the serum of immunized suckling mice, and the NtAb levels correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak in the immunized mice compared with those in Alum-only inoculated control mice. Elevated levels of interleukin-4, 6, interferon γ and tumour necrosis factor α were also observed in Alum-only control mice compared with immunized mice. Importantly, the virulent CV-A6 challenge strain was selected quickly and conveniently from a RD cell virus stock characterized with the natural multi-genotypes. The virulent determinants were mapped to V124M and I242 V at VP1. Together, our results indicated that this actively immunized mouse model is invaluable for future studies to develop multivalent vaccines containing the major component of CV-A6 against HFMD.

Efficacy of Coxsackievirus A5 Vaccine Candidates in an Actively Immunized Mouse Model.

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.

Pressure-induced amorphous zeolitic imidazole frameworks with reduced toxicity and increased tumor accumulation improves therapeutic efficacy In vivo.

Zeolitic Imidazole Frameworks (ZIFs) are widely applied in nanomedicine for their high drug loading, suitable pore size, pH-responsive drug release, and so on. However, fast drug release during circulation, unexpected toxicity to mice major organs, undesirable long-term accumulation in the lung and even death currently hinder their in vivo biomedical applications. Herein, we report an amorphous ZIF-8 (aZIF-8) with high loading of 5-Fu through pressure-induced amorphization. This nano-system avoids early drug release during circulation and provides tumor microenvironment-responsive drug release with improved in vitro cell viability, and survival rate in in vivo evaluations as compared to ZIF-8. Furthermore, aZIF-8 shows longer blood circulation and lower lung accumulation than ZIF-8 at same injected doses. Less drug release during circulation, longer blood circulation, and better biocompatibility of aZIF-8/5-Fu significantly improves its therapeutic efficacy in ECA-109 tumor-bearing mouse, and result in 100% survival rate over 50 days after treatment. Therefore, aZIF-8 with favorable biocompatibility and long blood circulation is expected to be a promising nano-system for efficacious cancer therapy in vivo.

Comparison of Two Surgical Epilation Procedures Based on the Nagata Method in All Degrees of Low Hairline Microtia.

Background: Various methods exist to manage unwanted hair in low hairline microtia. We present our 10-year experience that compares the two procedures toward all degrees of low hairline microtia. Methods: The tongue-shaped split-thickness skin graft procedure (modified Chen's procedure) and the modified Nagata procedure were used for ear reconstruction in 42 microtia patients with three degrees of low hairlines from 2010 to 2020. Hair follicles in the low hairline area were removed free-hand, and the removed area was replaced with extended temporoparietal fascia (TPF) flap during the ear elevation. The satisfaction score and the clearance percentages of the hair were used as outcome measures. Results: There was no significant difference in satisfaction scores and the hair clearance percentages of hair between two procedures (p > 0.05) and among three degrees of low hairline (p > 0.05), respectively. Although the complication rate showed no significant difference, the major types of complication in modified Chen's procedure was fluid accumulation (9.52%), whereas in modified Nagata procedure was hypertrophic scar (4.76%). Conclusion: Patients with low hairlines can be treated using two different microtia reconstruction techniques to limit hair growth on the new ear. The rib graft construct is covered by a TPF flap, which is then grafted with an ultrathin skin graft and shows benefit in this review of our 10-year experience. Clinical Trial Registration Information Provided: Registration no. and date registered: ChiCTR2000030214.

Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China.

Coxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.

Ten-Gram-Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis.

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T1 contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten-gram-scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd-salicylate nanoparticles, GdSalNPs-rBSA) with high r1 value of 19.51 mm-1 s-1 and very low r2 /r1 ratio of 1.21 (B0 = 1.5 T) for high-contrast T1 -weighted MRI of tumors. The GdSalNPs-rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t1/2 = 6.13 h), almost no Gd3+ release, and excellent biosafety. Moreover, the GdSalNPs-rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal-to-noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.

Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma.

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (i.e., high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthesized in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]}2) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (r1 = 60.8 mM-1 s-1, r2/r1 = 1.1). The maximum signal enhancement (ΔSNR) for T1-weighted MRI of tumors reached up to 423 ± 42% at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (<80%). ES-GON-rBSA-LF-RGD2 exhibited high biocompatibility and can transport across the in vitro BBB model and the in vivo BBB of mice due to its small particle size (dh = 13.4 nm) and LF receptor mediated transcytosis. Orthotopic GBM studies reinforce that ES-GON-rBSA3-LF-RGD2 can accumulate in the orthotopic GBM and enhance the radiation therapy of GBM as an effective radiosensitizing agent.

Carbon Dots as Fluorescent/Colorimetric Probes for Real-Time Detection of Hypochlorite and Ascorbic Acid in Cells and Body Fluid.

Hypochlorite (ClO-) and ascorbic acid (AA) are reported to have a high correlation with oxidative stress and related diseases, so it is necessary and critical to develop sensitive and fast response sensors to investigate the dynamical variation of these redox substances, especially those sensors which can detect ClO- and AA in real time in two manners. However, it is still an unmet challenge for now. Herein, novel carbon dots (RD-CDs) which can respond to ClO- and AA rapidly, reversibly, and dynamically by fluorescence and colorimetry were synthesized. In the fluorescence manner, the constructed nanosensor possessed high selectivity toward ClO- in the range of 0.1-100 µM with a detection limit of 83 nM, and can be selectively recovered by AA. It endows this sensor with good capacity as a fluorescent probe for dynamic detection of ClO- and AA in living cells, which can be monitored by a fluorescence microscope. In the colorimetric manner, ClO- and AA can be detected by UV-vis in the range of 5-200 µM and 1-30 µM, respectively. The concentrations of ClO- and AA in humor can be measured by RD-CDs in both fluorescence and colorimetric mode. The results above-mentioned demonstrate its great potential in biosensing.

Manganese-Zeolitic Imidazolate Frameworks-90 with High Blood Circulation Stability for MRI-Guided Tumor Therapy.

Zeolitic imidazolate frameworks (ZIFs) as smart drug delivery systems with microenvironment-triggered release have attracted much attention for tumor therapy. However, the exploration of ZIFs in biomedicine still encounters many issues, such as inconvenient surface modification, fast drug release during blood circulation, undesired damage to major organs, and severe in vivo toxicity. To address the above issues, we developed an Mn-ZIF-90 nanosystem functionalized with an originally designed active-targeting and pH-responsive magnetic resonance imaging (MRI) Y1 receptor ligand [Asn28, Pro30, Trp32]-NPY (25-36) for imaging-guided tumor therapy. After Y1 receptor ligand modification, the Mn-ZIF-90 nanosystem exhibited high drug loading, better blood circulation stability, and dual breast cancer cell membrane and mitochondria targetability, further favoring specific microenvironment-triggered tumor therapy. Meanwhile, this nanosystem showed promising T1-weighted magnetic resonance imaging contrast in vivo in the tumor sites. Especially, this nanosystem with fast clean-up had almost no obvious toxicity and no damage occurred to the major organs in mice. Therefore, this nanosystem shows potential for use in imaging-guided tumor therapy.