Heat-resistant boron-nitrogen doped lignin-derived adsorbent-catalyst for gaseous aromatic pollutants removal.

Lignin-based carbon material can be utilized as carbonaceous adsorbents for the removal of toxic gaseous organic pollutants, while the poor heat-resistance limited its widely application. Here in, B-N co-doped lignin carbon (BN-C) with high thermal stability was synthesized, and the optimized BN-C (1:2) exhibited notably improved heat resistance with the decomposition temperature up to 505 °C, and excellent adsorption capacity for o-dichlorobenzene (o-DCB) (1510.0 mg/g) and toluene (947.3 mg/g), together with good cyclic stability over 10 cycles for o-dichlorobenzene. The existence of abundant hexagonal boron nitride (h-BN) with good thermal conductivity contributed to the superior heat-resistance of BN-C (1:2), and the high specific surface area (1764.5 m2/g), enriched hydroxyl functional groups and improved graphitization degree contributed to its enhanced adsorption performance. More importantly, BN-C (1:2) supported Ru could effectively remove o-DCB and toluene at wide temperature range (50-300 °C). The present work guided the development of heat-resistant lignin-derived adsorbent-catalyst for gaseous aromatic pollutants removal, which benefits both environmental protection and resource utilization.

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

Exploring the chemical compositions of Fufang Yinhua Jiedu granules based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry combined with multistage intelligent data annotation strategy.

Fufang Yinhua Jiedu granules (FYJG) is a Traditional Chinese Medicine (TCM) compound formulae preparation comprising ten herbal drugs, which has been widely used for the treatment of influenza with wind-heat type and upper respiratory tract infections. However, the phytochemical constituents of FYJG have rarely been reported, and its constituent composition still needs to be elucidated. The complexity of the natural ingredients of TCMs and the diversity of preparations are the major obstacles to fully characterizing their constituents. In this study, an innovative and intelligent analysis strategy was built to comprehensively characterize the constituents of FYJG and assign source attribution to all components. Firstly, a simple and highly efficient ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MSE) method was established to analyze the FYJG and ten single herbs. High-accuracy MS/MS data were acquired under two collision energies using high-definition MSE in the negative and positive modes. Secondly, a multistage intelligent data annotation strategy was developed and used to rapidly screen out and identify the compounds of FYJG, which was integrated with various online software and data processing platforms. The in-house chemical library of 2949 compounds was created and operated in the UNIFI software to enable automatic peak annotation of the MSE data. Then, the acquired MS data were processed by MS-DIAL, and a feature-based molecular networking (FBMN) was constructed on the Global Natural Product Social Molecular Networking (GNPS) to infer potential compositions of FYJG by rapidly classifying and visualizing. It was simultaneously using the MZmine software to recognize the source attribution of ingredients. On this basis, the unique chemical categories and characteristics of herbaceous plant species are utilized further to verify the accuracy of the source attribution of multi-components. This comprehensive analysis successfully identified or tentatively characterized 279 compounds in FYJG, including flavonoids, phenolic acids, coumarins, saponins, alkaloids, lignans, and phenylethanoids. Notably, twelve indole alkaloids and four organic acids from Isatidis Folium were characterized in this formula for the first time. This study demonstrates a potential superiority to identify compounds in complex TCM formulas using high-definition MSE and computer software-assisted structural analysis tools, which can obtain high-quality MS/MS spectra, effectively distinguish isomers, and improve the coverage of trace components. This study elucidates the various components and sources of FYJG and provides a theoretical basis for its further clinical development and application.

Trends in cancer mortality among the elderly in China, 2005-2035.

BACKGROUND: With the appearance and aggravation of the aging society, cancer has become one of the major problems that threaten the life and health of Chinese residents seriously. OBJECTIVE: To explore the cancer epidemiological characteristics among the elderly in China from 2005 to 2016, and to provide strategies for cancer prevention and treatment. METHODS: Stratified analysis was conducted on the cancer mortality data of the elderly aged ≥60 years in China, which were selected from the Chinese Cancer Registry Annual Report. Joinpoint regression model was used to calculted average annual percentage change (AAPC) to estimate the time trends. Age-period-cohort (APC) model was used to explore the age, period and birth cohort effect on the risk of cancer death. Bayesian age-period-cohort (BAPC) model was used to predict trends in cancer mortality among elderly by gender and region to 2035. RESULTS: 2005-2016, cancer mortality in the elderly in China showed a decreasing trend (AAPC = -1.2%, P<0.001). Cancer mortality in rural areas was higher than that in urban areas, but the urban-rural difference gradually narrowed (t = 6.1, P<0.01). The APC model showed that cancer mortality increased with age. The relative risk (RR) for the period effect decreased. RR was lower for the later- born cohort than that for the earlier-born cohort in rural areas. Lung cancer mortality ranked first in both male and female, and showed an increasing trend among female in the 60-64, 80-84 and ≥85 age groups (AAPC60-64 = 1.0%, AAPC80-84 = 0.8%, AAPC≥85 = 2.0%, all P<0.05). By 2035, cancer mortality for the elderly was predicted to decline nationally, by sex and in rural areas, while rising in urban areas. CONCLUSION: Cancer mortality in the elderly in China showed a decreasing trend from 2005 to 2016, but it was still higher than the world average. Early cancer screening is important, especially in the elderly male and in rural areas.

Altered Expression of PDE4 Genes in Schizophrenia: Insights from a Brain and Blood Sample Meta-Analysis and iPSC-Derived Neurons.

Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their genetic association and function in cognitive processes such as long-term potentiation. We conducted a systematic gene expression meta-analysis of four PDE4 genes (PDE4A-D) in 10 brain sample datasets (437 samples) and three blood sample datasets (300 samples). Subsequently, we measured mRNA levels in iPSC-derived hippocampal dentate gyrus neurons generated from fibroblasts of three groups: healthy controls, healthy monozygotic twins (MZ), and their MZ siblings with schizophrenia. We found downregulation of PDE4B in brain tissues, further validated by independent data of the CommonMind consortium (515 samples). Interestingly, the downregulation signal was present in a subgroup of the patients, while the others showed no differential expression or even upregulation. Notably, PDE4A, PDE4B, and PDE4D exhibited upregulation in iPSC-derived neurons compared to healthy controls, whereas in blood samples, PDE4B was found to be upregulated while PDE4A was downregulated. While the precise mechanism and direction of altered PDE4 expression necessitate further investigation, the observed multilevel differential expression across the brain, blood, and iPSC-derived neurons compellingly suggests the involvement of PDE4 genes in the pathophysiology of schizophrenia.

Copper-Catalyzed Site-Selective Electrophilic Aromatic Alkylation of Monosubstituted Simple Arenes.

A copper-catalyzed highly para-selective electrophilic aromatic alkylation of monosubstituted simple arenes has been accomplished. This method provides a practical platform for the transformation from simple commercial arenes to well-defined di- and multisubstituted aromatics with high added value. Control experiments and DFT calculations reveal that the achievement of the excellent site-selectivity is ascribed to the controlled deprotonation of the Wheland intermediates. Remarkably, the type of alkylating regent has been shown to have a significant impact on site-selectivity.

Successful treatment of Bowen's Disease in the nipple-areola complex with a combination of photodynamic therapy and cryotherapy-A case report.

Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.

Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoid transplanted in mouse brain.

Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.

Transformation pathways of enrofloxacin chlorination disinfection by-products in constructed wetlands.

Antibiotic residues and their chlorinated disinfection by-products (Cl-DBPs) have adverse effects on organisms in aquaculture water. Taking enrofloxacin (ENR) as target antibiotic, this study investigated the degradation and transformation of ENR Cl-DBPs in constructed wetlands (CWs). Results showed that, ENR and its Cl-DBPs affected the biodegradation of CWs at the preliminary stage, but did not affect the adsorption by plant roots, substrates, and biofilms. The piperazine group of ENR had great electronegativity, and was prone to electrophilic reactions. The carboxyl on quinolone group of ENR had strong nucleophilicity, and was prone to nucleophilic reactions. C atoms with significant negative charges on the aromatic structure of quinolone group were prone to halogenation. During the chlorination of ENR, one pathway was the reaction of quinolone group, in which nucleophilic substitution reaction by chlorine occurred at C26 atom on carboxyl group, then halogenation occurred under the action of Cl+ at C17 site on the aromatic ring; the other pathway was the reaction of piperazine group, in which N7 atom was firstly attacked by HOCl, resulting in piperazine ring cleavage, then followed by deacylation, dealkylation, and halogenation. During the biodegradation of ENR Cl-DBPs, the reactivity of piperazine structure was strong, especially at N6, N7, C13, and C14 sites, while the ring structure of quinolone group was quite stable, and only occurred decyclopropyl at N5 site. Overall, the biodegradation of ENR Cl-DBPs in CWs went through processes including piperazine ring cleavage, tertiary amine splitting, dealkylation, and aldehyde oxidation under the action of coenzymes, in which metabolites such as ketones, aldehydes, carboxylic acids, amides, primary amines, secondary amines, tertiary amines and acetaldehyde esters were produced. Most ENR Cl-DBPs had greater bioaccumulation potential and stronger toxicity than their parent compound, fortunately, CWs effectively reduced the environmental risk of ENR Cl-DBPs through the cooperation of adsorption and biodegradation.

AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation.

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAVMUSE-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.

Photodynamic therapy combined with CO2 laser for the treatment of seborrheic keratosis in the auricle: A case report.

Seborrheic keratosis(SK) is a very common skin tumor which is mostly frequently observed in the trunck, head, neck. SK in the auricle is rare and this condition should be excluded the possibility of malignancy by pathologic diagnosis. We report a case of 66-year-old man who presented with a brownish, papillomatous, verrucous mass in the auricle for the past seven years, which began to growing faster during the previous year. Dermoscopy and histopathological examination were performed and the patient was diagnosed with SK. He was treated with the carbon dioxide(CO2) laser and aminolevulinate photodynamic therapy (ALA-PDT). The CO2 laser was used for the removal of the thick hypertrophic lesions and to enhance the transdermal absorption efficiency of ALA. A 20% ALA cream(118 mg/cm2) was applied to his lesion and sealed for 3 h without light, followed by irradiation with 630-nm LED light (96 J/cm2, 80 mw/cm2). We use fluorescent diagnosis with aminolevulinic acid to define the tumor margins at the first session of ALA-PDT. After 4 sessions of ALA-PDT, the lesion was completely removed and did not recur. Therefore, we consider that ALA-PDT combined with CO2 laser is a safe and effective choice for the treatment of seborrheic keratosis in the auricle.

Sulfadiazine chlorination disinfection by-products in constructed wetlands: Identification of biodegradation products and inference of transformation pathways.

Disinfection by-products (DBPs) formed from chlorination of antibiotics have greater toxicity than their parent compounds. Herein, this study investigated the biotransformation process of sulfadiazine Cl-DBPs in constructed wetlands (CWs). Results showed that, S atom on sulfonyl group, and N atoms on primary and secondary amine groups were the most reactive sites of sulfadiazine molecule. S1-N4 and S1-C8 of sulfadiazine are the most vulnerable bonds to cleave, followed by C14-N4 and C11-N5 bonds. In the chlorination process, sulfadiazine went through C-N bond cleavage, N-reductive alkylation, halogenation, and desulfonation to produce two aromatic Cl-DBPs. In the biodegradation process in CWs, sulfadiazine Cl-DBPs went through processes mainly including dechlorination, S-N bond cleavage, aniline-NH2 oxidation, desulfonation, phenol-OH oxidation, benzene ring cleavage, C-N bond cleavage, and ß-oxidation of fatty acids under the action of a variety of oxidoreductases and hydrolases, during which a total of ten biodegradation products was identified. Moreover, sulfadiazine affected the biodegradation rather than the adsorption process in CWs. The two aromatic sulfadiazine Cl-DBPs had much higher bioaccumulation potentials than their parent sulfadiazine, but for the ten biodegradation products of sulfadiazine Cl-DBPs in CWs, 70% and almost 100% of them had lower bioaccumulation potentials than sulfadiazine and their parent sulfadiazine Cl-DBPs, respectively. The CWs were effective in reducing the environmental risk of sulfadiazine Cl-DBPs.

Designing Peptide-Based Nanoinhibitors of Programmed Cell Death Ligand 1 (PD-L1) for Enhanced Chemo-immunotherapy.

The combination of immune checkpoint blockade (ICB) and chemotherapy has shown significant potential in the clinical treatment of various cancers. However, circulating regeneration of PD-L1 within tumor cells greatly limits the efficiency of chemo-immunotherapy and consequent patient response rates. Herein, we report the synthesis of a nanoparticle-based PD-L1 inhibitor (FRS) with a rational design for effective endogenous PD-L1 suppression. The nanoinhibitor is achieved through self-assembly of fluoroalkylated competitive peptides that target PD-L1 palmitoylation. The FRS nanoparticles provide efficient protection and delivery of functional peptides to the cytoplasm of tumors, showing greater inhibition of PD-L1 than nonfluorinated peptidic inhibitors. Moreover, we demonstrate that FRS synergizes with chemotherapeutic doxorubicin (DOX) to boost the antitumor activities via simultaneous reduction of PD-L1 abundance and induction of immunogenic cell death in murine colon tumor models. The nano strategy of PD-L1 regulation present in this study is expected to advance the development of ICB inhibitors and overcome the limitations of conventional ICB-assisted chemo-immunotherapy.

Chalcone-derivative L6H21 attenuates the OVA-induced asthma by targeting MD2.

Asthma represents a significant global challenge that affects individuals across all age groups and imposes substantial social and economic burden. Due to heterogeneity of the disease, not all patients obtain benefit with current treatments. The objective of this study was to explore the impact of MD2 on the progression of asthma using L6H21, a novel MD2 inhibitor, to identify potential targets and drug candidates for asthma treatment. To establish an asthma-related murine model and evaluate the effects of L6H21, ovalbumin (OVA) was used to sensitize and challenge mice. Pathological changes were examined with various staining techniques, such as H&E staining, glycogen staining, and Masson staining. Inflammatory cell infiltration and excessive cytokine secretion were evaluated by analyzing BALF cell count, RT-PCR, and ELISA. The TLR4/MD2 complex formation, as well as the activation of the MAPK and NF-кB pathways, was examined using western blot and co-IP. Treatment with L6H21 demonstrated alleviation of increased airway resistance, lung tissue injury, inflammatory cell infiltration and excessive cytokine secretion triggered by OVA. In addition, it also ameliorated mucus production and collagen deposition. In the L6H21 treatment group, inhibition of MAPK and NF-кB activation was observed, along with the disruption of TLR4/MD2 complex formation, in contrast to the model group. Thus, L6H21 effectively reduced the formation of the MD2 and TLR4 complex induced by OVA in a dose-dependent manner. This reduction resulted in the attenuation of MAPKs/NF-κB activation, enhanced suppression of inflammatory factor secretion, reduced excessive recruitment of inflammatory cells, and ultimately mitigated airway damage. MD2 emerges as a crucial target for asthma treatment, and L6H21, as an MD2 inhibitor, shows promise as a potential drug candidate for the treatment of asthma.

Core-shell structured carbon dots with up-conversion fluorescence and photo-triggered nitric oxide-releasing properties.

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.

Hybrid Manta Ray Foraging Algorithm with Cuckoo Search for Global Optimization and Three-Dimensional Wireless Sensor Network Deployment Problem.

In this paper, a new hybrid Manta Ray Foraging Optimization (MRFO) with Cuckoo Search (CS) algorithm (AMRFOCS) is proposed. Firstly, quantum bit Bloch spherical coordinate coding is used for the initialization of the population, which improves the diversity of the expansion of the traversal ability of the search space. Secondly, the dynamic disturbance factor is introduced to balance the exploratory and exploitative search ability of the algorithm. Finally, the unique nesting strategy of the cuckoo and Levy flight is introduced to enhance the search ability. AMRFOCS is tested on CEC2017 and CEC2020 benchmark functions, which is also compared and tested by using different dimensions and other state-of-the-art metaheuristic algorithms. Experimental results reveal that the AMRFOCS algorithm has a superior convergence rate and optimization precision. At the same time, the nonparametric Wilcoxon signed-rank test and Friedman test show that the AMRFOCS has good stability and superiority. In addition, the proposed AMRFOCS is applied to the three-dimensional WSN coverage problem. Compared with the other four 3D deployment methods optimized by metaheuristic algorithms, the AMRFOCS effectively reduces the redundancy of sensor nodes, possesses a faster convergence speed and higher coverage and then provides a more effective and practical deployment scheme.

Split-Cas9-based targeted gene editing and nanobody-mediated proteolysis-targeting chimeras optogenetically coordinated regulation of Survivin to control the fate of cancer cells.

BACKGROUND: Precise regulation of partial critical proteins in cancer cells, such as anti-apoptotic proteins, is one of the crucial strategies for treating cancer and discovering related molecular mechanisms. Still, it is also challenging in actual research and practice. The widely used CRISPR/Cas9-based gene editing technology and proteolysis-targeting chimeras (PROTACs) have played an essential role in regulating gene expression and protein function in cells. However, the accuracy and controllability of their targeting remain necessary. METHODS: Construction of UMUC-3-EGFP stable transgenic cell lines using the Sleeping Beauty system, Flow cytometry, quantitative real-time PCR, western blot, fluorescence microplate reader and fluorescence inverted microscope analysis of EGFP intensity. Characterization of Survivin inhibition was done by using Annexin V-FITC/PI apoptosis, calcein/PI/DAPI cell viability/cytotoxicity assay, cloning formation assay and scratch assay. The cell-derived xenograft (CDX) model was constructed to assess the in vivo effects of reducing Survivin expression. RESULTS: Herein, we established a synergistic control platform that coordinated photoactivatable split-Cas9 targeted gene editing and light-induced protein degradation, on which the Survivin gene in the nucleus was controllably edited by blue light irradiation (named paCas9-Survivin) and simultaneously the Survivin protein in the cytoplasm was degraded precisely by a nanobody-mediated target (named paProtacL-Survivin). Meanwhile, in vitro experiments demonstrated that reducing Survivin expression could effectively promote apoptosis and decrease the proliferation and migration of bladder cancerous cells. Furthermore, the CDX model was constructed using UMUC-3 cell lines, results from animal studies indicated that both the paCas9-Survivin system and paProtacL-Survivin significantly inhibited tumour growth, with higher inhibition rates when combined. CONCLUSIONS: In short, the coordinated regulatory strategies and combinable technology platforms offer clear advantages in controllability and targeting, as well as an excellent reference value and universal applicability in controlling the fate of cancer cells through multi-level regulation of key intracellular factors.

Biotransformation and Gut Microbiota-Mediated Bioactivity of Flavonols.

Consumption of fruits and vegetables has been associated with a reduced risk of multiple diseases, such as metabolic disorders. Flavonols are the most ubiquitous flavonoids in fruits and vegetables. However, dietary flavonols exhibit a general low oral bioavailability for their extensive biotransformation mediated by phase II enzymes in enterocytes and liver as well as by microbiota in the gut lumen. In this context, flavonols have brought attention to a paradox between low bioavailability and health-promoting effects. Flavonols are often transformed prior to absorption, which could change their biological activity. Compared to their parent compounds, the corresponding metabolites of flavonols in vivo might exhibit similar or higher intrinsic bioactivities, or perhaps a decreased efficacious effectiveness. Indeed, a growing body of evidence from biological function studies of metabolites supports the positive and significant contribution of in vivo metabolic processes, particularly conversion mediated by gut microbiota, to the health-promoting benefits of flavonols. As such, further understanding of the metabolic fate of flavonols and biological activities of their metabolites as well as the possible impact of microbiota-mediated conversion on the bioactivity is of great significance to guide a rational diet with flavonol-rich fruits and vegetables and/or flavonol-containing functional foods.

Transplantation Strategies to Enhance Maturity and Cellular Complexity in Brain Organoids.

Human brain organoids are 3-dimensional cell aggregates that are generated from pluripotent stem cells and recapitulate features of the early developing human brain. Brain organoids mainly consist of cells from the neural lineage, such as neural progenitor cells, neurons, and astrocytes. However, current brain organoid systems lack functional vasculature as well as other non-neuronal cells that are indispensable for oxygen and nutrient supply to the organoids, causing cell stress and formation of a necrotic center. Attempts to utilize intracerebral transplantation approaches have demonstrated successful vascularization of brain organoids and robust neurodifferentiation. In this review, we summarize recent progress and discuss ethical considerations in the field of brain organoid transplantation.