The impact of mold exposure on anxiety symptoms in the older adults: A moderated mediation model based on CLHLS.

BACKGROUND: Mold exposure is a common environmental issue that can adversely affect health, particularly among older adults. The impact of mold exposure on anxiety symptoms in this population has not been extensively studied. OBJECTIVE: This study aims to examine the relationship between mold exposure and anxiety symptoms in older adults, considering the mediating role of cognitive function and the moderating effects of open window ventilation and multivitamin supplementation. METHODS: Data from the eighth wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) was utilized, including 11,021 participants aged 65 and older. Logistic regression models and moderated mediation analysis were employed to explore these relationships. RESULTS: Mold exposure was significantly associated with increased anxiety symptoms (OR=1.831, 95 % CI=1.588-2.110). Cognitive impairment partially mediated this relationship. Open window ventilation (B=-0.040, P<0.001) and multivitamin supplementation (B=-0.197, P<0.001) served as protective factors. Subgroup analysis indicated higher vulnerability among females (OR=1.72, P<0.001), those aged 65-79 (OR=1.86, P<0.001), urban residents (OR=2.50, P<0.001), individuals not living with family members (OR=1.89, P<0.001), those with higher education (OR=2.01, P<0.001), married individuals (OR=1.80, P<0.001), and those in very good health (OR=2.11, P=0.026). CONCLUSION: Mold exposure contributes to anxiety symptoms in older adults, with cognitive decline playing a mediating role. Effective interventions, including improved ventilation and multivitamin supplementation, can mitigate these effects. These findings highlight the need for targeted public health strategies to enhance the well-being of older adults.

Target Recognition-Triggered Peroxidase-Mimicking Activity Depression in Homochiral Nanochannels for Identifying Cystine Enantiomers.

Enantioselective identification of chiral molecules is of paramount importance in medical science, biochemistry, and pharmaceutics owing to the configuration-dependent activities of enantiomers. However, the identical physicochemical properties of enantiomers remain challenging in chiral sensing. In this study, inspired by the peroxidase-mimicking activity of Fe(III)-based nanomaterials, an enantioselective artificial architecture is constructed on TiO2 nanochannels. Homochiral Ti-based metal-organic frameworks (MOFs) use a 2,2'-bipyridine-5,5'-dicarboxylic acid ligand as the artificial enzyme skeleton, Fe(III) as peroxidase-mimicking centers, and l-tartaric acid (TA) as a chiral recognition selector. Using l-/d-cystine as model enantiomers, the chiral moieties of l-TA on Ti-MOFs allow stereoselective recognition of guest molecules through hydrogen bonds formed between chiral cystine and the host. In a tris(2-carboxyethyl)phosphine hydrochloride-containing environment, the disulfide bonds in cystine molecules are further cleaved, and the HS-tails react with Fe(III) active sites, causing the loss of peroxidase-like performance of nanochannels. Benefitting from the nanochannel architecture's current-potential (I-V) properties, the selective recognition of cystine enantiomers is directly monitored through the peroxidase-like activity change-induced ionic current signatures. This study provides a new and universal strategy for distinguishing disulfide- and thiol-containing chiral molecules.

Enantioselective Target Transport-Mediated Nanozyme Decomposition for the Identification of Reducing Enantiomers in Asymmetric Nanochannel Arrays.

Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent effects on biological systems. In this study, we developed an electrochemical platform based on a tandem recognition-reaction zone design in TiO2 nanochannels for the specific recognition of reducing enantiomers. In this system, MIL-125(Ti) Ti-metal-organic frameworks, in situ grown in TiO2 nanochannels, provided a homochiral recognition environment via postmodification with l-tartaric acid (l-TA); MnO2 nanosheets possessing both glucose oxidase (GOD)- and peroxidase (POD)-mimicking activities served as the target-reactive zone at the end of the nanochannels. The use of penicillamine (Pen) enantiomers as model-reducing targets facilitated the passage of d-Pen through the homochiral recognition zone, owing to its lower affinity with l-TA. The passed Pen molecules reached the responsive zone and induced a target concentration-dependent MnO2 disassembly. Such target recognition event impaired the cascade GOD- and POD-like activities of MnO2. Combining the enantioselectivity of the recognition nanochannels with the cascade enzyme-like activity of MnO2 toward glucose and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate), the quantitative identification of l- and d-Pen was achieved through the changes in transmembrane ionic current induced by the generated charged products. This recognition-reaction zone design paves an effective way for developing a promising electrochemical platform for the identification of reducing enantiomers with improved selectivity and sensitivity.

Target-Modulated Hydrophobic Precipitation in Photocatalytic Nanochannels for Sensitive Detection of Alpha Fetoprotein.

It is important to detect cancer biomarkers at an early stage of tumor development for the effective diagnosis and treatment of cancer. As a well-known probe for detecting superoxide (·O2-) radicals, nitro blue tetrazolium (NBT) can rapidly react with ·O2- to form a hydrophobic formazan precipitate. In this study, by deliberately utilizing this reaction, Pt asymmetrically decorated on a TiO2 nanochannel membrane (Pt/TiNM) is explored to fabricate an electrochemical immunosensing platform with outstanding selectivity and ultrahigh sensitivity. Using NBT as the substrate, hydrophobic formazan precipitation induces a substantial block of ionic diffusion flux in nanochannels. Using alpha fetoprotein (AFP) as the target analyte, the established immunorecognition event was used to induce MoS2-Ab2 conjugates. Thanks to the excellent light-shielding ability of MoS2 nanosheets, the production of ·O2- radicals from the photocatalysis of Pt/TiNM is effectively depressed because of the attenuated arrival of light. The reduced formazan precipitation results in ionic transport changes in nanochannels, which in turn enables the selective recognition of AFP down to 2 ng mL-1. This target-modulated sensing strategy is also capable of sensing other immune targets, thus paving a new way for designing nanochannel-based sensing platforms.

Nucleation and dissociation of methane clathrate embryo at the gas-water interface.

Among natural energy resources, methane clathrate has attracted tremendous attention because of its strong relevance to current energy and environment issues. Yet little is known about how the clathrate starts to nucleate and disintegrate at the molecular level, because such microscopic processes are difficult to probe experimentally. Using surface-specific sum-frequency vibrational spectroscopy, we have studied in situ the nucleation and disintegration of methane clathrate embryos at the methane-gas-water interface under high pressure and different temperatures. Before appearance of macroscopic methane clathrate, the interfacial structure undergoes 3 stages as temperature varies, namely, dissolution of methane molecules into water interface, formation of cage-like methane-water complexes, and appearance of microscopic methane clathrate, while the bulk water structure remains unchanged. We find spectral features associated with methane-water complexes emerging in the induction time. The complexes are present over a wide temperature window and act as nuclei for clathrate growth. Their existence in the melt of clathrates explains why melted clathrates can be more readily recrystallized at higher temperature, the so-called "memory effect." Our findings here on the nucleation mechanism of clathrates could provide guidance for rational control of formation and disintegration of clathrates.

Construction of Peroxidase-like Metal-Organic Frameworks in TiO2 Nanochannels: Robust Free-Standing Membranes for Diverse Target Sensing.

The high cost and easy denaturation of natural enzymes under environmental conditions hinder their practical usefulness in sensing devices. In this study, peroxidase (POD)-like metal-organic frameworks (MOFs) were in situ grown in the nanochannels of an anodized TiO2 membrane (TiO2NM) as an electrochemical platform for multitarget sensing. By directly using a nanochannel wall as the precursor of metal nodes, Ti-MOFs were in situ derived on the nanochannel wall. Benefitting from the presence of bipyridine groups on the ligands, the MOFs in the nanochannels provide plenty of sites for Fe3+ anchoring, thus endowing the resulting membrane (named as Fe3+:MOFs/TiO2NM) with remarkable POD-like activity. Such Fe3+-induced POD-like activity is very sensitive to thiol-containing molecules owing to the strong coordination effect of thiols on Fe3+. Most importantly, the POD-like activity of nanochannels can be in situ characterized by the current-potential (I-V) properties via catalyzing the oxidation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) substrate to the corresponding positively charged product ABTS•+. As a proof-of-concept application, the free-standing POD-like membranes were applied as a label-free assay in sensing cysteine, as well as monitoring acetylcholinesterase (AChE) activity through the generated thiol-containing product. Furthermore, based on the toxicity effect of organophosphorus (OP) compounds on AChE, the robust membranes were successfully utilized to evaluate the toxicity of diverse OP compounds. The POD-like nanochannels open up an innovative way to expand the application of nanochannel-based electrochemical sensing platforms in drug inspection, food safety, and environmental pollution.

Biomineralization-Driven Ion Gate in TiO2 Nanochannel Arrays for Cell H2S Sensing.

The level of hydrogen sulfide in the brain and vasculature has long been associated with human health and diseases. Hence, simple and robust analytical tools allowing determination of hydrogen sulfide levels are highly desirable. In this work, a biomineralization-driven ion gate in TiO2 nanochannel arrays for H2S sensing was designed and developed. The formed CuS precipitation decreased the transmembrane current in the presence of bovine serum albumin used as biological mineralizer. Label-free assay for sensing of intracellular S2- was achieved based on changes in ionic current with a detection limit of 56 MCF-7 cells. More importantly, the proposed sensing strategy was promising for reusable application through dissolution of CuS in an acidic media (pH = 1).

Structure of the submonolayer of ethanol adsorption on a vapor/fused silica interface studied with sum frequency vibrational spectroscopy.

Sum-frequency vibrational spectroscopy in the CH and OH stretch region was used to study ethanol adsorption on fused silica from vapor of different ethanol partial pressures. It was found that the adsorbed ethanol molecules were oriented with their methyl group tilted away from the surface normal by an average angle of ∼45° at low ethanol vapor pressures and ∼39° when approaching saturated vapor pressure. The spectral change with ethanol vapor pressure and the deduced adsorption isotherm show that ethanol molecules have two distinct adsorption sites on silica: One is the silanol group site to which an ethanol molecule can be strongly hydrogen-bonded, and the other is the siloxane (Si-O-Si) group site to which an ethanol molecule can be weakly bonded. The presence of water in vapor significantly reduced the surface coverage of ethanol on silica due to competitive adsorption between ethanol and water.

Investigation of the Source of Snoring Sound by Drug-Induced Sleep Nasendoscopy.

OBJECTIVE: To investigate the source of snoring sound in patients with simple snoring (SS) and different degrees of obstructive sleep apnea syndrome (OSAS) in order to provide a basis for the surgical treatment of snoring. METHODS: Fifty-two patients with either SS or OSAS (with an apnea-hypopnea index ≤40) underwent drug-induced sleep nasendoscopy (DISN). Vibration sites in the pharyngeal cavity were observed. RESULTS: Vibration of the soft palate, pharyngeal lateral wall, epiglottis, and tongue base appeared in 100, 53.8, 42.3, and 26.9% of the patients, respectively. The source of snoring sound was divided into two types: palatal fluttering only (type I) and multisite vibration (type II). The latter was divided into 3 subtypes: palatal fluttering with epiglottis vibration (type IIa), palatal fluttering with lateral wall vibration (type IIb), and palatal fluttering with vibration of the lateral wall, epiglottis, and tongue base together (type IIc). The distribution of type I snoring was the highest in SS patients. Type IIb was more common in patients with medium and severe OSAS. Type IIc was most common in patients with severe OSAS. CONCLUSION: The source of snoring sound is diverse, with SS and OSAS patients showing different features. DISN is a very effective method of identifying the snoring source.

[Association between some factors in maternal pregnancy and childhood asthma with an onset before 3 years of age].

OBJECTIVE: To study the association between some factors in maternal pregnancy and childhood asthma with an onset before 3 years of age, and to provide a basis for the prevention and treatment of childhood asthma and further research on its pathogenesis. METHODS: A retrospective clinical epidemiological study was carried out in 100 children with asthma (age of onset<3 years) and 100 children without allergic disease who were randomly selected as controls. The related information of children and mothers was investigated by questionnaire survey, including general information, medical history, personal and family allergic history, perinatal data, and mothers' health and lifestyle during their pregnancy such as diet, disease, and environmental exposure. The main survey indices were preliminarily analyzed, selected, and assigned, and then the data were subjected to univariate and multivariate logistic regression analyses. RESULTS: The univariate and multivariate logistic regression analyses showed that the fetal sex, history of atopic disease before pregnancy, history of respiratory infection in pregnancy, and the intake of fish, shrimp, crab, meat and spicy food in pregnancy were significantly associated with childhood asthma with an onset before 3 years of age, with odds ratios of 2.868, 5.051, 4.640, 3.746, 2.971, 3.075, and 2.225, respectively. CONCLUSIONS: Many factors in maternal pregnancy are associated with childhood asthma with an onset before 3 years of age, and the risk of which can be reduced by the prevention of respiratory infection and appropriate diet in pregnancy.

Urban resilience reduces depressive symptoms among middle-aged and elderly adults: A multidimensional analysis based on China longitudinal healthy longevity survey.

With the rapid urbanization and aging population, depression has become a severe public health issue globally, affecting millions of individuals and significantly impacting their quality of life and healthcare costs. Urban resilience refers to a city's ability to absorb, recover, and prepare for future shocks, ensuring sustainable development despite challenges. This study aims to explore the impact of urban resilience on depressive symptoms among middle-aged and elderly adults. Using data from the China Health and Retirement Longitudinal Study (CHARLS), we analyzed five dimensions of urban resilience: economic, social, ecological, institutional, and infrastructural resilience. The results of cox proportional hazards model indicate that high levels of urban resilience significantly reduce the risk of depressive symptoms (HR = 0.875, 95% CI: 0.832-0.920, P < 0.001). Specifically, economic resilience (HR = 0.883, 95% CI: 0.846-0.921, P < 0.001), social resilience (HR = 0.916, 95% CI: 0.876-0.958, P < 0.001), ecological resilience (HR = 0.670, 95% CI: 0.516-0.869, P = 0.003), institutional resilience (HR = 0.922, 95% CI: 0.886-0.960, P < 0.001), and infrastructural resilience (HR = 0.875, 95% CI: 0.826-0.926, P < 0.001) all show significant negative correlations with depressive symptoms. Furthermore, the mitigation of depressive symptoms risk resulting from improved urban resilience disproportionately benefits vulnerable groups and those with healthy living habits. These findings provide scientific evidence for urban planning and policy formulation, contributing to the promotion of mental health and healthy aging among middle-aged and elderly populations.

[Advances in the Separation and Removal of Microplastics in Water Treatment Processes].

In this review, we comprehensively analyzed the distribution of microplastics （MPs） in major water ecosystems in China and the fate of MPs during the water treatment process. The removal efficiency of MPs with different colors, sizes, shapes, and materials was also discussed. The results showed that the abundance of microplastics in the aquatic environment was geographically variable and closely related to human activities. Fibrous and transparent （white） microplastics were the most common features in China's water ecosystems and water treatment plants, with polypropylene （PP）, polyethylene （PE）, and polystyrene （PS） being the most common polymer types of microplastics. The removal efficiency of MPs varied from different treatment processes significantly. Pre-treatment and primary treatment in wastewater treatment plants （WWTPs） contributed the most to the removal. In the secondary treatment, the sedimentation tank showed more efficiency than the biological treatment processes. Tertiary treatment processes demonstrated remarkable effectiveness in achieving terminal control of MPs, especially membrane technologies. On the contrary, aeration and hydrodynamic effects may have increased the abundance of MPs in WWTPs. In drinking water treatment plants （DWTPs）, coagulation-sedimentation processes were found to be the most effective in removing MPs, followed by filtration and disinfection processes. Further, both pre-treatment and post-treatment steps also made significant contributions to MPs removal.

[Effects of nasal cavity enlarging surgery on snoring in obstructive sleep apnea hypopnea syndrome patients].

OBJECTIVE: To explore the efficacies of nasal cavity enlarging surgery in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with nasal obstruction. METHODS: From April 2011 to October 2012, a total of 22 OSAHS patient with nasal obstruction underwent nasal cavity enlargement. Natural overnight snoring was digitally recorded, polysomnography (PSG) performed simultaneously and nasal resistance measured at pre- and post-operation. Body mass index (BMI), Epworth sleepiness scale (ESS), apnea-hypopnea index (AHI), minimum oxygen saturation SaO2, total nasal resistance, peak frequency, maximal frequency, mean frequency, central frequency and power ratio 800 Hz of snores were recorded and compared. RESULTS: BMI and SaO2 rose while AHI and ESS declined post-operatively. No statistical difference existed between pre-operation and post-operation. The total nasal resistance was (0.39 ± 0.15) and (0.29 ± 0.11) Pa·cm(-3)·s(-1) at pre- and post-operation. And there was significant statistical difference (P < 0.01) . The snores at pre- and post-operation exhibited different patterns in time and power spectrum distribution domains. And fmax, fpeak and fmean declined while fc and PR800 rose at post-operation. Significant statistical differences existed in the change of fpeak and PR800 at pre- and post-operation (P < 0.01) . CONCLUSION: Nasal cavity enlargement can lessen nasal resistance and change the acoustic characteristics of snoring in OSAHS patients. The postoperative snoring focus of lower frequency suggests that acoustic parameters of snores may be used to evaluate the efficacy of OSAHS surgery.

From growth to sustainability: investigating N-shaped EKC and the role of energy productivity, technological advancement, and human capital in OECD economies.

Environmental degradation rates have been on a concerning upward trajectory in recent decades, directly threatening the well-being of global populations. Responding to this urgent matter, scholars have been driven to explore its nuances, particularly emphasizing lowering energy consumption and carbon emissions amidst the growing demands of growing economies. Achieving the targets outlined in the 2015 Paris Climate Agreement has also become a priority for many countries. Therefore, this study scrutinizes the Environmental Kuznets Curve (EKC) hypothesis, specifically focusing on the role of energy productivity, technological advancement, and human capital in fostering a sustainable environment across 35 OECD economies from 1990 to 2018. Utilizing three robust econometric techniques, Cross-Sectional Autoregressive Distributed Lag (CS-ARDL), Fully Modified Ordinary Least Squares (FMOLS), and Dynamic Ordinary Least Squares (DOLS), we have drawn insightful conclusions from our data. The analysis substantiates an N-shaped EKC hypothesis relationship between GDP and CO2 emissions, pointing towards an initially increasing, then decreasing, and finally an increasing again trend of emissions with GDP. Furthermore, the long-term projections underscore that energy productivity, technological progression, and human capital formation harm the environment. These findings culminate in a call for governments to orchestrate extensive plans and initiatives. This involves promoting green technologies, renewable energy-based ideas, and comprehensive education and awareness programs. These efforts should span all educational levels, highlighting climate change, sustainable practices, and the need for CO2 reduction, empowering societies to contribute to a sustainable future.

Long-term average spectrum measures of consecutive snore sounds from different sources determined by drug-induced sleep endoscopy.

STUDY OBJECTIVES: The goal of this study was to investigate the value of the long-term average spectrum in the acoustic analysis of snore sounds arising from different sources in the upper airway. METHODS: Long-term average spectrum was used to analyze sequences of 10 consecutive snore sounds that had been divided into 2 groups, soft-palate type and lateral-wall type, according to the vibration site generating the snore sounds and the patterns of soft tissue collapse in the upper airway as identified by drug-induced sleep endoscopy. We calculated the first spectral peak, mean spectral energy, high-frequency energy, 0-1 kHz spectral energy, 1-5 kHz spectral energy, and 0-1 kHz/1-5 kHz difference from each group and compared the differences between them. RESULTS: All parameters except mean spectral energy showed significant differences between the 2 groups. The first spectral peak of less than 265.53 Hz, and the 0-1k/1-5 kHz difference of less than -11.6 dB strongly suggests soft-palate-type snore sounds. CONCLUSIONS: Long-term average spectrum has potential application for snore sound source identification. We recommend using first spectral peak and a 0-1 kHz/1-5 Hz difference to identify soft-palate-type snore sounds. CITATION: Peng H, Xu H, Xu Z, Jia R, Yu H. Long-term average spectrum measures of consecutive snore sounds from different sources determined by drug-induced sleep endoscopy. J Clin Sleep Med. 2023;19(1):145-150.

Target-modulated mineralization of wood channels as enzyme-free electrochemical sensors for detecting amyloid-ß species.

Alzheimer's disease (AD) is an irreversible brain disorder, which has been found to be associated with neurotoxic amyloid-ß oligomers (AßO). The early diagnosis of AD is still a great challenge. Herein, inspired by the hierarchical channel structure of natural wood, we design and demonstrate a low-cost and sensitive wood channel-based fluidic membrane for electrochemical sensing of AßO1-42. In this design, Zn/Cu-2-methylimidazole (Zn/Cu-Hmim) with artificial peroxidase (POD)-like activity was asymmetrically fabricated at one side of the wood channels by biomimetic mineralization and a subsequent ion exchange reaction. The strong affinity between Cu(II) and AßO1-42 enables Cu(II) species in Zn/Cu-Hmim to be extracted by AßO1-42, thus suppressing the POD-like performance via Zn/Cu-Hmim disassembly. Using Zn/Cu-Hmim to catalyze the oxidation reaction of 2,2'-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) by H2O2, the current-voltage (I-V) properties of wood channels are influenced by the generated oxidation product (ABTS•+), thus providing information useful for the quantitative analysis of AßO1-42. Importantly, the three aggregation states of Aß1-42 (AßM1-42, AßO1-42, and AßF1-42) can also be identified, owing to the affinity difference and available reaction sites. The proposed wood membrane provides a novel, assessable, and scalable channel device to develop sensitive electrochemical sensors; moreover, the sustainable wood materials represent alternative candidates for developing channel-structured sensing platforms.

Rational design of mesoporous chiral MOFs as reactive pockets in nanochannels for enzyme-free identification of monosaccharide enantiomers.

Monosaccharides play significant roles in daily metabolism in living organisms. Although various devices have been constructed for monosaccharide identification, most rely on the specificity of the natural enzyme. Herein, inspired by natural ionic channels, an asymmetrical MOF-in-nanochannel architecture is developed to discriminate monosaccharide enantiomers based on cascade reactions by combining oxidase-mimicking and Fenton-like catalysis in homochiral mesoporous CuMOF pockets. The identification performance is remarkably enhanced by the increased oxidase-mimicking activity of Au nanoparticles under a local surface plasmon resonance (LSPR) excitation. The apparent steady-state kinetic parameters and nano-fluidic simulation indicate that the different affinities induced by Au-LSPR excitation and the confinement effect from MOF pockets precipitate the high chiral sensitivity. This study offers a promising strategy for designing an enantiomer discrimination device and helps to gain insight into the origin of stereoselectivity in a natural enzyme.

Metal organic frameworks-in-nanochannels: A tailorable chromatography membrane for isolation of target protein.

Metal-organic frameworks (MOFs) demonstrate strong potential in biosample separation. However, the obtained MOFs powders are unsuitable for recovery techniques in an aqueous solution, especially the challenges of withdrawing MOFs particles and expanding their functions for specific applications. Herein, a general strategy is designed utilizing metal oxide-nanochannel arrays as precursors and templates for in-situ selective growth of MOFs structures. The exemplary MOFs (Ni-bipy) with tailored composition are selectively grown in NiO/TiO2 nanochannel membrane (NM) using NiO as the sacrificial precursor, which enables one to achieve a ∼262 times concentration of histidine-tagged proteins within 100 min. The significantly improved adsorption efficiency in a wide pH range and the effective enrichment from a complex matrix as a nanofilter illustrate the great potential of MOFs in nanochannels membranes for the high-efficiency recovery of essential proteins in complex biological samples. The porous self-aligned Ni-MOFs/TiO2 NM exhibits biocompatibility and flexible functionalities, which is desirable for the generation of multifunctional nanofilter devices and developing biomacromolecule delivery vehicles.

Sensor fault detection and minimum detectable fault analysis for dynamic point-the-bit rotary steerable system.

In this paper, the sensor fault detection problem considering the drilling disturbances is studied for the dynamic point-the-bit rotary steerable system. Firstly, the DPRSS is modeled as a linear system with the drilling disturbances, including unknown inputs, measurement noises, and model perturbations. Then, a finite-frequency zonotopic fault detection observer is proposed. The finite-frequency range H- performance and the P-radius criterion are considered to design the observer gains such that the residuals are sensitive to sensor faults and robust against the drilling disturbances simultaneously. Subsequently, the calculation method of minimum detectable faults is presented for the proposed sensor fault detection mechanism. Finally, simulations and experiments are presented to illustrate the effectiveness of the proposed methods.

Melanin-gelatin nanoparticles with both EPR effect and renal clearance for PA/MRI dual-modal imaging of tumors.

As cancer nanotherapeutics, the ideal multifunctional nanoparticles not only have the processing ability to accumulate effectively in tumors, but also can be excreted rapidly from the body via renal clearance after effective treatment. Melanin is an endogenous biological material, and gelatin has natural biocompatibility and biodegradability. Such materials are more promising in the development of diagnostic and therapeutic nanoplatform for future clinical translation. In this study, we have developed a kind of size-shrinkable PA/MRI theranostic agent based on gelatin fabricated ultrasmall melanin nanoparticles (MNPs-GNP). The MNPs-GNP nanoparticles, with a size of about 100 nm, presented good dispersibility, broadband light absorbance, negligible cellular cytotoxicity, preferable tumor accumulation by EPR-based passive targeting. The dual-modal imaging results showed that the nanoparticles have excellent photoacoustic (PA) imaging and nuclear magnetic resonance (MRI) imaging after tumor-bearing mice were intravenously injected with MNPs-GNP. Additionally, gelatin is the substrate of matrix metalloproteinase-2 (MMP-2), following with the degradation of gelatin nanoparticles by MMP-2, the large-size MNPs-GNP turns to be small-size melanin, which could mainly be excreted via renal clearance avoiding potential toxicity to body tissues. These preliminary results indicated that MNPs-GNP can overcome the dilemma between EPR and renal clearance, which has clinical application potentiality as a PA/MRI dual-modal candidate agent for cancer theranostics.