Melanopsin retinal ganglion cells mediate light-promoted brain development.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.

Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis.

During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.

Deep annotation of long noncoding RNAs by assembling RNA-seq and small RNA-seq data.

Long noncoding RNAs (lncRNAs) are increasingly being recognized as modulators in various biological processes. However, due to their low expression, their systematic characterization is difficult to determine. Here, we performed transcript annotation by a newly developed computational pipeline, termed RNA-seq and small RNA-seq combined strategy (RSCS), in a wide variety of cellular contexts. Thousands of high-confidence potential novel transcripts were identified by the RSCS, and the reliability of the transcriptome was verified by analysis of transcript structure, base composition, and sequence complexity. Evidenced by the length comparison, the frequency of the core promoter and the polyadenylation signal motifs, and the locations of transcription start and end sites, the transcripts appear to be full length. Furthermore, taking advantage of our strategy, we identified a large number of endogenous retrovirus-associated lncRNAs, and a novel endogenous retrovirus-lncRNA that was functionally involved in control of Yap1 expression and essential for early embryogenesis was identified. In summary, the RSCS can generate a more complete and precise transcriptome, and our findings greatly expanded the transcriptome annotation for the mammalian community.

Anisotropic Charge Migration on Perovskite Oxysulfide for Boosting Photocatalytic Overall Water Splitting.

The synthesis of photocatalysts with both broad light absorption and efficient charge separation is significant for a high solar energy conversion, which still remains to be a challenge. Herein, a narrow-bandgap Y2Ti2O5S2 (YTOS) oxysulfide nanosheet coexposed with defined {101} and {001} facets synthesized by a flux-assisted solid-state reaction was revealed to display the character of an anisotropic charge migration. The selective photodeposition of cocatalysts demonstrated that the {101} and {001} surfaces of YTOS nanosheets were the reduction and oxidation regions during photocatalysis, respectively. Density functional theory (DFT) calculations indicated a band energy level difference between the {101} and {001} facets of YTOS, which contributes to the anisotropic charge migration between them. The exposed Ti atoms on the {101} surface and S atoms on the {001} surface were identified, respectively, as reducing and oxidizing centers of YTOS nanosheets. This anisotropic charge migration generated a built-in electric field between these two facets, quantified by spatially resolved surface photovoltage microscopy, the intensity of which was found to be highly correlated with photocatalytic H2 production activity of YTOS, especially exhibiting a high apparent quantum yield of 18.2% (420 nm) after on-site modification of a Pt@Au cocatalyst assisted by Na2S-Na2SO3 hole scavengers. In conjunction with an oxygen-production photocatalyst and a [Co(bpy)3]2+/3+ redox shuttle, the YTOS nanosheets achieved a solar-to-hydrogen conversion efficiency of 0.15% via a Z-scheme overall water splitting. Our work is the first to confirm anisotropic charge migration in a perovskite oxysulfide photocatalyst, which is crucial for enhancing charge separation and surface catalytic efficiency in this material.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

Nonreciprocal optomechanically induced transparency and enhanced ground-state cooling in a reversed-dissipation cavity system.

We explore the prospects of phase-modulated optical nonreciprocity and enhanced ground-state cooling of a mechanical resonator for the reversed-dissipation system, where the dissipative coupling between two cavities is realized through the adiabatic elimination of a low-Q mechanical mode, while a high-Q mechanical mode interacts with two mutually coupled cavities, forming a closed-loop structure. This unique system facilitates the nontrivial phenomenon of optomechanically induced transparency (OMIT), which exhibits asymmetry due to the frequency shift effect. We also observe the emergence of parity-dependent unidirectional OMIT windows (appearing under the phase-matching condition), which can be dynamically modulated by both the phase factors and the strength of the dissipative coupling. Furthermore, our study delves into the ground-state cooling effect operating within the reversed-dissipation regime. Intriguingly, the cooling effect can be significantly enhanced by carefully engineering dissipative complex coupling, such as in the phase-matching condition. The potential applications of this scheme extend to the fabrication of ideal optical isolators in optical communication systems and the manipulation of macroscopic mechanical resonators at the quantum level, presenting exciting opportunities in quantum technologies.

Genetically Proxied Sarcopenia-Related Muscle Traits and Depression: Evidence from the FinnGen Cohort.

BACKGROUND: Sarcopenia and depression are common and often coexist in the elderly. This study aims to determine the impact of sarcopenia-related muscle traits on depression. METHODS: A two-sample Mendelian randomization (MR) study was performed on the summary-level data from the FinnGen cohort to estimate the causal association of appendicular lean mass (ALM), walking pace, or low hand grip strength with depression. Additionally, multivariable MR (MVMR) was performed to assess the dependence of each muscle trait in the causality and adjust the effect of body mass index (BMI). Supplementary backward MR analyses were performed to estimate the effect of depression on sarcopenia-related muscle traits. RESULTS: Univariable MR analyses demonstrated that there were causal associations of ALM (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.88-0.99), walking pace (OR: 0.53; 95% CI: 0.32-0.88), and low hand grip strength (OR: 1.20; 95% CI: 1.05-1.38) with depression. MVMR analyses showed that ALM was the only trait that had a significant causal relationship with depression (OR: 0.91; 95% CI: 0.85-0.98) after accounting for the other two muscle traits. Moreover, the independent association of ALM with depression remained (OR: 0.92; 95% CI: 0.85-0.99) after being adjusted by BMI. The backward MR analyses showed no causal associations of depression with any sarcopenia-related muscle traits. CONCLUSION: Low muscle mass independently increases the risk of depression. This study determined the muscle-related risk factors of depression, which may help establish the causality between sarcopenia and depression and provide evidence-based recommendations for improving mental health in the elderly.

Exploring the stability and aromaticity of rare earth doped tin cluster MSn16- (M = Sc, Y, La).

Rare earth elements have high chemical reactivity, and doping them into semiconductor clusters can induce novel physicochemical properties. The study of the physicochemical mechanisms of interactions between rare earth and tin atoms will enhance our understanding of rare earth functional materials from a microscopic perspective. Hence, the structure, electronic characteristics, stability, and aromaticity of endohedral cages MSn16- (M = Sc, Y, La) have been investigated using a combination of the hybrid PBE0 functional, stochastic kicking, and artificial bee colony global search technology. By comparing the simulated results with experimental photoelectron spectra, it is determined that the most stable structure of these clusters is the Frank-Kasper polyhedron. The doping of atoms has a minimal influence on density of states of the pure tin system, except for causing a widening of the energy gap. Various methods such as ab initio molecular dynamics simulations, the spherical jellium model, adaptive natural density partitioning, localized orbital locator, and electron density difference are employed to analyze the stability of these clusters. The aromaticity of the clusters is examined using iso-chemical shielding surfaces and the gauge-including magnetically induced currents. This study demonstrates that the stability and aromaticity of a tin cage can be systematically adjusted through doping.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Optogenetic activation of the lateral habenulaD1R-ventral tegmental area circuit induces depression-like behavior in mice.

A number of different receptors are distributed in glutamatergic neurons of the lateral habenula (LHb). These glutamatergic neurons are involved in different neural pathways, which may identify how the LHb regulates various physiological functions. However, the role of dopamine D1 receptor (D1R)-expressing habenular neurons projecting to the ventral tegmental area (VTA) (LHbD1R-VTA) remains not well understood. In the current study, to determine the activity of D1R-expressing neurons in LHb, D1R-Cre mice were used to establish the chronic restraint stress (CRS) depression model. Adeno-associated virus was injected into bilateral LHb in D1R-Cre mice to examine whether optogenetic activation of the LHb D1R-expressing neurons and their projections could induce depression-like behavior. Optical fibers were implanted in the LHb and VTA, respectively. To investigate whether optogenetic inhibition of the LHbD1R-VTA circuit could produce antidepressant-like effects, the adeno-associated virus was injected into the bilateral LHb in the D1R-Cre CRS model, and optical fibers were implanted in the bilateral VTA. The D1R-expressing neuronal activity in the LHb was increased in the CRS depression model. Optogenetic activation of the D1R-expressing neurons in LHb induced behavioral despair and anhedonia, which could also be induced by activation of the LHbD1R-VTA axons. Conversely, optogenetic inhibition of the LHbD1R-VTA circuit improved behavioral despair and anhedonia in the CRS depression model. D1R-expressing glutamatergic neurons in the LHb and their projections to the VTA are involved in the occurrence and regulation of depressive-like behavior.

Lifestyle factors and subacromial impingement syndrome of the shoulder: potential associations in finnish participants.

BACKGROUND: Emerging evidence has indicated the associations between subacromial impingement syndrome (SIS) of shoulder and lifestyle factors. However, whether unhealthy lifestyle factors causally increase SIS risk is not determined. This study aims to evaluate whether lifestyle factors are the risk factors of SIS. METHODS: A two-sample Mendelian randomization (MR) study was designed to evaluate the effect of 11 lifestyle factors on SIS risk. Causality was determined using the inverse-variance weighted method to calculate the odds ratio (OR) and establish a 95% confidence interval (CI). Weighted median method, MR-Egger method and MR-PRESSO method were conducted as sensitivity analysis. RESULTS: Four lifestyle factors were identified causally associated with an increased risk of SIS using the IVW method: insomnia (OR: 1.66 95% CI 1.38, 2.00; P = 8.86 × 10- 8), short sleep duration (OR: 1.53 95% CI 1.14, 2.05: P = 0.0043), mobile phone usage (OR: 4.65, 95% CI 1.59, 13.64; P = 0.0051), and heavy manual or physical work (OR: 4.24, 95% CI 2.17, 8.26; P = 2.20 × 10- 5). Another causal but weak association was found between smoking initiation on SIS (OR: 1.17, 95% CI 1.01, 1.35; P = 3.50 × 10- 2). Alcohol, coffee consumption, physical activity, sedentary behavior, sleep duration and computer usage were not found to be causally associated with an increased risk of SIS. Sensitivity analyses indicated that the MR estimates were robust and no heterogeneity and pleiotropy were identified in these MR analyses. CONCLUSION: Sleep habits and shoulder usage were identified as causal factors for SIS. This evidence supports the development of strategies aimed at improving sleep behaviors and optimizing shoulder usage patterns as effective measures to prevent SIS.

Exploring the environmental factor fulvic acid attenuates the ecotoxicity of graphene oxide under food delivery exposure.

There is limited understanding of nanoparticle potential ecotoxicity, particularly regarding the influence of environmental factors that can be transferred through the food chain. Here, we assessed the transfer behavior and the ecotoxicity of commercially manufactured graphene oxide nano-materials (GO, <100 nm) in a food chain perspective spanning from Escherichia coli (E. coli) to Caenorhabditis elegans (C. elegans) under simulated environmental conditions. Our findings revealed that E. coli preyed upon GO, subsequently transferring it to C. elegans, with a discernible distribution of GO observed in the digestive system and reproductive system. Accumulated GO generated serious ecological consequences for the higher level of the food chain (C. elegans). More importantly, GO and the resulting injurious effects of germ cells could be transferred to the next generation, indicating that GO exposure could cause genetic damage across generations. Previous research has demonstrated that GO can induce degradation of both the inner and outer cell membranes of E. coli, which is then transmitted to C. elegans through the food chain. Additionally, fulvic acid (FA) possesses various functional groups that enable interaction with nanomaterials. Our findings indicated that these interactions could mitigate ecotoxicity caused by GO exposure via food delivery, and this approach could be extended to modify GO in a way that significantly reduced its toxic effects without compromising performance. These results highlighted how environmental factors could attenuate ecological risks associated with nanomaterial transmission through the food chain.

Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure-Activity Relationship Model.

The quantitative structure-activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r2) of 0.9836 and a cross-validated correlation coefficient (q2) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 µg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives.

eDNA reveals spatial homogenization of fish diversity in a mountain river affected by a reservoir cascade.

One of the main reasons for the decline in global freshwater biodiversity can be attributed to alterations in hydrological conditions resulting from dam construction. However, the majority of current research has focused on single or limited numbers of dams. Here, we carried out a seasonal fish survey, using environmental DNA (eDNA) method, on the Wujiang River mainstream (Tributaries of the Yangtze River, China) to investigate the impact of large-scale cascade hydropower development on changes in fish diversity patterns. eDNA survey revealed that native fish species have decreased in contrast to alien fish. There was also a shift in fish community structure, with declines of the dominant rheophilic fish species, an increase of the small-size fish species, and homogenization of species composition across reservoirs. Additionally, environmental factors, such as temperature, dissolved oxygen and reservoir age, had a significant effect on fish community diversity. This study provides basic information for the evaluation of the impact of cascade developments on fish diversity patterns.

Accuracy assessment between computer-guided surgery planning and actual tooth position during tooth autotransplantation.

BACKGROUND/AIM: This study aims to evaluate the precision and efficacy of utilizing computer-aided design (CAD) in combination with three-dimensional printing technology for tooth transplantation. MATERIAL AND METHODS: This study analysed 50 transplanted teeth from 48 patients who underwent tooth transplantation surgery with the aid of CAD and positional guides. A consistent coordinate system was established using preoperative and postoperative cone-beam computed tomography images. Linear displacements and angular deviations were calculated by identifying key regions in both virtual designs and actual transplanted teeth. Additionally, an analysis was conducted to explore potential factors influencing these deviations. RESULTS: The mean cervical deviation, apical deviation, and angular deviation among the 50 transplanted teeth were 1.16 ± 0.57 mm, 1.80 ± 0.94 mm, and 6.82 ± 3.14°, respectively. Cervical deviation was significantly smaller than apical deviation. No significant difference in deviation was observed among different recipient socket locations, holding true for both single-root, and multi-root teeth. However, a significant difference was noted in apical deviation between single-root and multi-root teeth. Our analysis identified a correlation between apical deviation and root length, leading to the development of a prediction model: Apical deviation = 0.1390 × (root length) + 0.2791. CONCLUSIONS: The postoperative position of the donor teeth shows discrepancies compared to preoperative simulation when utilizing CAD and 3D printed templates during autotransplantation procedures. Continual refinement of preoperative design is a crucial endeavour.

Rapid, Massive, and Green Synthesis of Polyoxometalate-Based Metal-Organic Frameworks to Fabricate POMOF/PAN Nanofiber Membranes for Selective Filtration of Cationic Dyes.

Developing high-efficiency membrane materials for the rapid removal of organic dyes is crucial but remains a challenge. Polyoxometalates (POMs) clusters with anionic structures are promising candidates for the removal of cationic dyes via electrostatic interactions. However, their shortcomings, such as their solubility and inability to be mass-produced, hinder their application in water pollution treatment. Here, we propose a simple and green strategy utilizing the room temperature stirring method to mass produce nanoscale polyoxometalate-based metal-organic frameworks (POMOFs) with porous rhomboid-shaped dodecahedral and hexagonal prism structures. The products were labeled as POMOF1 (POMOF-PW12) and POMOF2 (POMOF-PMo12). Subsequently, a series of x wt% POMOF1/PAN (x = 0, 3, 5, and 10) nanofiber membranes (NFMs) were prepared using electrospinning technology, where polyacrylonitrile (PAN) acts as a "glue" molecule facilitating the bonding of POMOF1 nanoparticles. The as-prepared samples were comprehensively characterized and exhibited obvious water stability, as well as rapid selective adsorption filtration performance towards cationic dyes. The 5 wt% POMOF1/PAN NFM possessed the highest removal efficiency of 96.7% for RhB, 95.8% for MB, and 86.4% for CV dyes, which realized the selective separation over 95% of positively charged dyes from the mixed solution. The adsorption mechanism was explained using FT-IR, SEM, Zeta potential, and adsorption kinetics model, which proved that separation was determined via electrostatic interaction, hydrogen bonding, and π-π interactions. Moreover, the POMOF1/PAN membrane presented an outstanding recoverable and stable removal rate after four cycles. This study provides a new direction for the systematic design and manufacture of membrane separation materials with outstanding properties for contaminant removal.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Green Synthesis of Carboxymethyl Chitosan-Based CuInS2 QDs with Luminescent Response toward Pb2+ Ion and Its Application in Bioimaging.

Polysaccharide-based QDs have attracted great attention in the field of biological imaging and diagnostics. How to get rid of the high heavy metal toxicity resulting from conventional Cd- and Pb-based QDs is now the main challenge. Herein, we offer a simple and environmentally friendly approach for the "direct" interaction of thiol-ending carboxymethyl chitosan (CMC-SH) with metal salt precursors, resulting in CuInS2 QDs based on polysaccharides. A nucleation-growth mechanism based on the LaMer model can explain how CMC-CuInS2 QDs are formed. As-prepared water-soluble CMC-CuInS2 QDs exhibit monodisperse particles with sizes of 5.5-6.5 nm. CMC-CuInS2 QDs emit the bright-green fluorescence at 530 nm when excited at 466 nm with the highest quantum yield of ∼18.0%. Meanwhile, the fluorescence intensity of CMC-CuInS2 QD aqueous solution is quenched with the addition of Pb2+ and the minimal limit of detection is as little as 0.4 nM. Furthermore, due to its noncytotoxicity, great biocompatibility, and strong biorecognition ability, CMC-CuInS2 QDs can be exploited as a possible cell membrane imaging reagent. The imaging studies also demonstrate that CMC-CuInS2 QDs are suitable for Pb2+ detection in live cells and living organisms (zebrafish). Thus, this work offers such an efficient, green, and practical method for creating low-toxicity and water-soluble QD nanosensors for a sensitive and selective detection of toxic metal ion in live cells and organisms.

Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging.

Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy.

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1ß-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable.