The effect of preterm birth on thalamic development based on shape and structural covariance analysis.

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

Research trends and hotspot analysis of age-related hearing loss: A bibliometric analysis from 2019 to 2023.

BACKGROUND: Age-related hearing loss (ARHL) - also termed presbycusis - is prevalent among older adults, leading to a range of issues. Although considerable progress in the understanding of ARHL over the decades, available reports lack data from recent years and do not comprehensively reflect the latest advancements and trends. Therefore, our study sought to assess research hotspots and trends in ARHL over the past 5 years to provide the basis for future research. MATERIALS AND METHODS: The Web of Science Core Collection database was searched and screened from January 1, 2019 to October 21, 2023, according to the inclusion criteria. CiteSpace (5.8.R3), VOSviewer (1.6.19), and Microsoft Excel 2019 were employed for bibliometric analysis and visualization. RESULTS: 3084 articles from 92 countries led by the United States and China were included. There has been a steady upward trend in the number of publications from 2019 to 2023. The most productive institutions, authors, and journals are Johns Hopkins University (n = 113), Lin FR (n = 66), and Ear and Hearing (n = 135), respectively. Trend topic analyses revealed that "cochlear synaptopathy" and "dementia" were the predominant foci. Keywords, including "individuals" and "national health", began to appear. CONCLUSION: Over the past 5 years, the annual number of publications has increased significantly and will continue to do so. Research on the mechanism of ARHL, represented by "oxidative stress", is a continuing focus. Emerging topics such as "individual differences" and "national health" may be potential future hotspots in this field.

Organic fertilizer substitution benefits microbial richness and wheat yield under warming.

Climate warming poses a serious threat to soil biodiversity and crop yield. Application of organic fertilizer has been extensively practiced to improve soil health and crop productivity. However, information is limited about the effects of organic fertilizer on microbial communities and diversity (richness) under warming. Thus, to investigate the interactive effects of temperature (ambient temperature and warming) and fertilizer (chemical fertilizer and partial substitution of chemical fertilizer with organic fertilizer) on microbial properties and wheat yield, a two-factorial pot experiment was conducted using soils with high and low fertility The results showed that warming and organic fertilizer had minor effects on bacterial Shannon and Simpson indexes. Due to concomitant reductions in soil moisture, warming decreased the average Chao index by 5.4 % and Ace index by 3.8 % for soils with high and low fertility (P < 0.05). High-throughput sequence presented that dominated genus was Bacillus with spore-forming ability. Under warming and drying conditions, microbes with adaptive traits (spore-forming ability) would outcompete the other microbes, and decrease microbial Chao and Ace index (richness). However, organic fertilizer counteracted the adverse effects of warming on microbial richness attributed to positive interaction between temperature and fertilizer on soil nutrients and organic carbon. The strong relationships between bacterial richness and wheat yield, as well as soil nutrients, highlighted the importance of soil biodiversity in improving soil nutrients and crop productivity. Partial substitution of chemical fertilizer with organic fertilizer significantly increased wheat yield by 27.1 % and 14.9 % under ambient temperature and by 28.0 % and 19.6 % under warming for soils with high and low fertility, respectively. Overall, this study provided the possibility to increase bacterial richness related to nutrient turnover and crop production by organic fertilizer application with reduced chemical fertilizer, especially under climate warming.

Catalytic [4+2]- and [4+4]-cycloaddition using furan-fused cyclobutanone as a privileged C4 synthon.

Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 µM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 = 0.89 ± 0.13 µM), respectively.

Temperature-driven divergence in molecular distribution and microbial invasion and the associated texture softening during dual-phase fermentation of Paocai.

Temperature is an important driving force that shapes the texture of fermented vegetables through driving the molecular distribution and microbial invasion between the liquid phase (brine) and the solid phase (vegetables) during fermentation. The objective of this study was to investigate the texture softening by investigating firmness, microstructure, physicochemical properties, molecular distribution and microbial community between brine and vegetables of Paocai as affected by fermentation temperatures of 10 °C, 20 °C and 30 °C. Results demonstrated that, compared with 10 °C and 30 °C, 20 °C attenuated softening of Paocai by restraining microbial invasion and suppressing pectinolysis. Moreover, at 20 °C, a balanced molecular distribution and microbial community were achieved between vegetables and brine, thus accomplishing acid-production fermentation. By contrast, 10 °C and 30 °C promoted nonfermentative microbial genera, retarding fermentation. This study provided an understanding of the divergent influence of temperature on quality formation of fermented vegetables during fermentation.

Harmonizing three-dimensional MRI using pseudo-warping field guided GAN.

In pursuit of cultivating automated models for magnetic resonance imaging (MRI) to aid in diagnostics, an escalating demand for extensive, multisite, and heterogeneous brain imaging datasets has emerged. This potentially introduces biased outcomes when directly applied for subsequent analysis. Researchers have endeavored to address this issue by pursuing the harmonization of MRIs. However, most existing image-based harmonization methods for MRI are tailored for 2D slices, which may introduce inter-slice variations when they are combined into a 3D volume. In this study, we aim to resolve inconsistencies between slices by introducing a pseudo-warping field. This field is created randomly and utilized to transform a slice into an artificially warped subsequent slice. The objective of this pseudo-warping field is to ensure that generators can consistently harmonize adjacent slices to another domain, without being affected by the varying content present in different slices. Furthermore, we construct unsupervised spatial and recycle loss to enhance the spatial accuracy and slice-wise consistency across the 3D images. The results demonstrate that our model effectively mitigates inter-slice variations and successfully preserves the anatomical details of the images during the harmonization process. Compared to generative harmonization models that employ 3D operators, our model exhibits greater computational efficiency and flexibility.

Discovery and Characterization of Pyridoxal 5'-Phosphate-Dependent Cycloleucine Synthases.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary amino acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), are useful building blocks for pharmaceuticals. In this study, starting with the biosynthesis of fusarilin A, we discovered a family of PLP-dependent enzymes that can facilitate tandem carbon-carbon forming steps to catalyze an overall [3 + 2]-annulation. In the first step, the cycloleucine synthases use SAM as the latent electrophile and an in situ-generated enamine as the nucleophile for γ-substitution. Whereas previously characterized γ-replacement enzymes protonate the resulting α-carbon and release the acyclic amino acid, cycloleucine synthases can catalyze an additional, intramolecular aldol or Mannich reaction with the nucleophilic α-carbon to form the substituted cyclopentane. Overall, the net [3 + 2]-annulation reaction can lead to 2-hydroxy or 2-aminocycloleucine products. These studies further expand the biocatalytic scope of PLP-dependent enzymes.

Construction of phase-separated Co/MnO synergistic catalysts and integration onto sponge for rapid removal of multiple contaminants.

Wastewater treatment recycling is critical to ensure safe water supply or to overcome water shortage. Herein, we developed metallic Co integration onto MnO nanorods (MON) resulting in a phase-separated synergetic catalyst by creating more Mn(III) via the Jahn-Teller effect and oxygen vacancies and improving the redox capability of Co nanoparticles mediated by a thin carbon layer. Additionally, the N-doped surface carbon network on MON contributes to polar sites, facilitating the enrichment of contaminants around reactive sites, thereby shortening the migration of reactive oxidative species (ROS) toward contaminants. The optimized MnO@Co/C-600 exhibits superior PMS activation efficiency for bisphenol A degradation (0.463 min-1), displaying nearly a 20-fold enhancement in the rate constant compared to Mn3O4/C-600. Subsequent experiments involving variable modulation and extension were conducted to further elucidate the multiple synergistic effects. The mechanism study further confirms the synergy of ˙SO4-, ˙OH, ˙O2-, and 1O2, along with additional electron transfer pathways. The intermediates generated during degradation pathways and their toxicity to aquatic organisms were identified. Notably, a monolith integrated catalyst was explored by anchoring MnO@Co/C-600 onto a tailored melamine sponge based on Ca ion triggered crosslink tactic for the photothermal degradation of bisphenol A, tetracycline and norfloxacin, endowed with easy recovery and good stability. Furthermore, we demonstrated that the total organic carbon removal of multiple contaminants surpassed that of sole contaminants.

A CuCo Bimetal Confined Hollow SiC Hybrid Photothermal Nanoreactor for the Integration of Pollutant Mineralization and Solar-Powered Water Evaporation.

Growing attention has been paid to the rational treatment of antibiotics-bearing medical wastewater. However, the complexity of polluted wastewater makes the later comprehensive treatment difficult only by the Advanced Oxidation Process technique. Therefore, the coupled water treatment techniques including contaminant mineralization and regeneration of cleanwater become very attractive. A bimetallic functional hollow nanoreactor defined as (Co@SiO2/Cu-X) was successfully constructed by coating a Cu-doped silica layer on the metal-organic framework (ZIF-67) followed by programmed calcination in nitrogen. The nanoreactor was endowed with a hollow configuration composed of mesoporous N-doping C-Silica hybrid shell encapsulated ultrafine Cu and Co metallic species. Such a configuration allows for the efficient diffusion and open reaction space of big contaminant molecules. The catalytic synergy of exposed Co-Cu bimetals and the easy accessibility of electron-rich contaminants by polar N doping sites triggered surface affinity make the optimal Co@SiO2/Cu-6 afford an excellent catalytic norfloxacin mineralization activity (7 min, kabs=0.744 min-1) compared to Cu-free Co@SiO2-6 (kabs=0.493 min-1) and Co-6 (kabs=0.378 min-1) Benefiting from the above unique advantages, Co@SiO2/Cu-6 show excellent removal performance in degrading different pollutants (carbamazepine, oxytetracycline, tetracycline, and bisphenol A) and persistent recycled stability in removing NFX. In addition, by virtue of the excellent photothermal properties, interfacial solar water evaporation application by Co@SiO2/Cu-6 was further explored to reach the regeneration of cleanwater (1.595 kg m-2 h-1, 97.51 %). The integration of pollutant mineralization and solar water evaporation by creating the monolith evaporation by anchoring the Co@SiO2/Cu-6 onto the tailored melamine sponge allows the regeneration of cleanwater (1.6 kg⋅m-2⋅h-1) and synchronous pollutant removal (NFX, 95 %, 60 min), which provides potential possibility the treatment of complicated wastewater.

Subclinical variations on ECG and their associations with structural brain aging networks.

Impaired cardiac function is associated with cognitive impairment and brain imaging features of aging. Cardiac arrhythmias, including atrial fibrillation, are implicated in clinical and subclinical brain injuries. Even in the absence of a clinical diagnosis, subclinical or prodromal substrates of arrhythmias, including an abnormally long or short P-wave duration (PWD), a measure associated with atrial abnormalities, have been associated with stroke and cognitive decline. However, the extent to which PWD has subclinical influences on overall aging patterns of the brain is not clearly understood. Here, using neuroimaging and ECG data from the UK Biobank, we use a novel regional "brain age" method to identify the brain aging networks associated with abnormal PWD. We find that PWD is inversely associated with accelerated brain aging in the sensorimotor, frontoparietal, ventral attention, and dorsal attention networks, even in the absence of overt cardiac diseases. These findings suggest that detrimental aging outcomes may result from subclinically abnormal PWD.

Monolithic Interphase Enables Fast Kinetics for High-Performance Sodium-Ion Batteries at Subzero Temperature.

In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310 mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.

Fast Na+ Kinetics and Suppressed Voltage Hysteresis Enabled by a High-Entropy Strategy for Sodium Oxide Cathodes.

O3-type layered transition metal cathodes are promising energy storage materials due to their sufficient sodium reservoir. However, sluggish sodium ions kinetics and large voltage hysteresis, which are generally associated with Na+ diffusion properties and electrochemical phase transition reversibility, drastically minimize energy density, reduce energy efficiency, and hinder further commercialization of sodium-ion batteries (SIBs). Here, this work proposes a high-entropy tailoring strategy through manipulating the electronic local environment within transition metal slabs to circumvent these issues. Experimental analysis combined with theoretical calculations verify that high-entropy metal ion mixing contributes to the improved reversibility of redox reaction and O3-P3-O3 phase transition behaviors as well as the enhanced Na+ diffusivity. Consequently, the designed O3-Na0.9Ni0.2Fe0.2Co0.2Mn0.2Ti0.15Cu0.05O2 material with high-entropy characteristic could display a negligible voltage hysteresis (<0.09 V), impressive rate capability (98.6 mAh g-1 at 10 C) and long-term cycling stability (79.4% capacity retention over 2000 cycles at 5 C). This work provides insightful guidance in mitigating the voltage hysteresis and facilitating Na+ diffusion of layered oxide cathode materials to realize high-rate and high-energy SIBs.

Correction: Dong et al. Identification of the Trace Components in BopuzongJian and Macleaya cordata Extract Using LC-MS Combined with a Screening Method. Molecules 2021, 26, 3851.

The article in question [...].

Polarization-Dependent Anisotropy of LIPSSs' Morphology Evolution on a Single-Crystal Silicon Surface.

Utilizing the principle of laser-induced periodic surface structures (LIPSSs), this research delves into the morphological evolution of single-crystal silicon surfaces irradiated by a near-infrared picosecond laser through a scanning mode. With the increase in laser energy density, the nanostructure morphology on single-crystal silicon surfaces induced by incident lasers with different polarization directions sequentially produces high spatial-frequency LIPSSs (HSFLs) with a period of 220 nm ± 10 nm parallel to the laser polarization, low spatial-frequency LIPSSs (LSFLs) with a period of 770 nm ± 85 nm perpendicular to the direction of the polarization, and groove structures. Furthermore, by varying the angle between the laser polarization and the scanning direction, the study examined the combined anisotropic effects of the laser polarization scanning direction angle and the laser polarization crystal orientation angle on the genesis of LIPSSs on single-crystal silicon (100) surfaces. The experiments revealed polarization-related anisotropic characteristics in the morphology of HSFLs. It was found that when the polarization angle approached 45°, the regularity of the LSFLs deteriorated, the modification width decreased, and the periodicity increased. This is critical for the precise control of the LSFLs' morphology.

Functionally responsive hydrogels with salt-alkali sensitivity effectively target soil amelioration.

The long-standing crisis of soil salinization and alkalization poses a significant challenge to global agricultural development. High soil salinity-alkalinity, water dispersion, and nutrient loss present major hurdles to soil improvement. Novel environmentally friendly gels have demonstrated excellent water retention and slow-release capabilities in agricultural enhancement. However, their application for improving saline-alkali soil is both scarce and competitive. This study proposes a new strategy for regulating saline-alkali soil using gel-coated controlled-release soil modifiers (CWR-SRMs), where radical-polymerized gels are embedded on the surface of composite gel beads through spray coating. Characterization and performance analysis reveal that the three-dimensional spatial network structure rich in hydrophilic groups exhibits good thermal stability (first-stage weight loss temperature of 257.7 °C in thermogravimetric analysis) and encapsulation efficiency for fulvic acid­potassium (FA-K), which can enhance soil quality in saline-alkali environments. The molecular chain relaxation under saline-alkali conditions promotes a synergistic effect of swelling and slow release, endowing it with qualifications as a water reservoir, Ca2+ source unit, and slow-release body. The results of a 6 weeks incubation experiment on 0-20 cm saline-alkaline soil with different application gradients showed that the gradient content had a significant effect on the soil improvement effect. Specifically, the T2 (the dosage accounted for 1 % of soil mass) treatment significantly increases water retention (30 % ~ 90 %), and nutrient levels (30 % ~ 50 %), while significantly decreasing soil sodium colloid content (30 % ~ 60 %) and soil pH (10 % ~ 15 %). Furthermore, PCA analysis indicates that the addition of 1 % CWR-SRMs as amendments can significantly adjust the negative aspects of soil salinity and alkalinity. This highlights the excellent applicability of CWR-SRMs in improving saline-alkali agricultural ecosystems, demonstrating the potential value of novel environmentally friendly gels as an alternative solution for soil challenges persistently affected by adverse salinity and alkalinity.

Optimized silicate nanozymes with atomically incorporated iron and manganese for intratumoral coordination-enhanced once-for-all catalytic therapy.

Although plant-derived cancer therapeutic products possess great promise in clinical translations, they still suffer from quick degradation and low targeting rates. Herein, based on the oxygen vacancy (OV)-immobilization strategy, an OV-enriched biodegradable silicate nanoplatform with atomically dispersed Fe/Mn active species and polyethylene glycol modification was innovated for loading gallic acid (GA) (noted as FMMPG) for intratumoral coordination-enhanced multicatalytic cancer therapy. The OV-enriched FMMPG nanozymes with a narrow band gap (1.74 eV) can be excited by a 650 nm laser to generate reactive oxygen species. Benefiting from the Mn-O bond in response to the tumor microenvironment (TME), the silicate skeleton in FMMPG collapses and completely degrades after 24 h. The degraded metal M (M = Fe, Mn) ions and released GA can in situ produce a stable M-GA nanocomplex at tumor sites. Importantly, the formed M-GA with strong reductive ability can transform H2O2 into the fatal hydroxyl radical, causing serious oxidative damage to the tumor. The released Fe3+ and Mn2+ can serve as enhanced contrast agents for magnetic resonance imaging, which can track the chemodynamic and photodynamic therapy processes. The work offers a reasonable strategy for a TME-responsive degradation and intratumoral coordination-enhanced multicatalytic therapy founded on bimetallic silicate nanozymes to achieve desirable tumor theranostic outcomes.

Parvalbumin and Somatostatin: Biomarkers for Two Parallel Tectothalamic Pathways in the Auditory Midbrain.

The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain's tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.

Theoretical insights into the mechanism underlying aflatoxin B1 transformation by the BsCotA-methyl syringate system.

Global concern exists regarding the contamination of food and animal feed with aflatoxin B1 (AFB1), which poses a threat to the health of both humans and animals. Previously, we found that a laccase from Bacillus subtilis (BsCotA) effectively detoxified AFB1 in a reaction mediated by methyl syringate (MS), although the underlying mechanism has not been determined. Therefore, our primary objective of this study was to explore the detoxification mechanism employed by BsCotA. First, the enzyme and mediator dependence of AFB1 transformation were studied using the BsCotA-MS system, which revealed the importance of MS radical formation during the oxidation process. Aflatoxin Q1 (AFQ1) resulting from the direct oxidation of AFB1 by BsCotA, was identified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results of UPLC-MS/MS and density functional theory calculations indicated that the products included AFQ1, AFB1-, and AFD1-MS-coupled products in the BsCotA-MS system. The toxicity evaluations revealed that the substances derived from the transformation of AFB1 through the BsCotA-MS mechanism exhibited markedly reduced toxicity compared to AFB1. Finally, we proposed a set of different AFB1-transformation pathways generated by the BsCotA-MS system based on the identified products. These findings greatly enhance the understanding of the AFB1-transformation mechanism of the laccase-mediator system.

Targeted Delivery of Active Sites by Oxygen Vacancy-Engineered Bimetal Silicate Nanozymes for Intratumoral Aggregation-Potentiated Catalytic Therapy.

Biodegradable silicate nanoconstructs have aroused tremendous interest in cancer therapeutics due to their variable framework composition and versatile functions. Nevertheless, low intratumoral retention still limits their practical application. In this study, oxygen vacancy (OV)-enriched bimetallic silicate nanozymes with Fe-Ca dual active sites via modification of oxidized sodium alginate and gallic acid (GA) loading (OFeCaSA-V@GA) were developed for targeted aggregation-potentiated therapy. The band gap of silica markedly decreased from 2.76 to 1.81 eV by codoping of Fe3+ and Ca2+, enabling its excitation by a 650 nm laser to generate reactive oxygen species. The OV that occurred in the hydrothermal synthetic stage of OFeCaSA-V@GA can anchor the metal ions to form an atomic phase, offering a massive fabrication method of single-atom nanozymes. Density functional theory results reveal that the Ca sites can promote the adsorption of H2O2, and Fe sites can accelerate the dissociation of H2O2, thereby realizing a synergetic catalytic effect. More importantly, the targeted delivery of metal ions can induce a morphological transformation at tumor sites, leading to high retention (the highest retention rate is 36.3%) of theranostic components in tumor cells. Thus, this finding may offer an ingenious protocol for designing and engineering highly efficient and long-retention nanodrugs.