Stabilizing Dye-Sensitized Upconversion Hybrids by Cyclooctatetraene.

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert low-energy near-infrared (NIR) light into high-energy visible light, making them valuable for broad applications. UCNPs often suffer from poor light-harvesting capabilities, which can be significantly improved by incorporating organic dye antennas. However, the dye-sensitized upconversion systems are prone to severe photobleaching in an ambient atmosphere. Here, we present a synergistic approach to mitigate photobleaching by introducing triplet state quencher cyclooctatetraene (COT). COT effectively suppresses the generation of singlet oxygen by quenching the triplet states of the dye and consumes the existing singlet oxygen through oxidant reactions. The inclusion of COT extends the half-life of IR806 by 4.7-times by preventing the oxidation of its poly(methylene) chains. Without significantly affecting emission intensity and dynamics, COT effectively stabilized dye-UCNPs, demonstrating a notable 3.9-fold increase in half-life under continuous laser irradiation. Our findings suggest a new strategy to enhance the photostability of near-infrared dyes and dye-sensitized upconversion nanohybrids.

Insight into endophytic microbial diversity in two halophytes and plant beneficial attributes of Bacillus swezeyi.

This study utilized high-throughput sequencing to investigate endophytic bacteria diversity in halophytic plants Anabasis truncate (AT) and Anabasis eriopoda (AE) from the Aral Sea region. Following sequence processing, 356 Amplicon Sequence Variants (ASVs) were discovered. The abundance and variety of endophytic bacteria were higher in AT. Bacillota, Pseudomonadota, Actinomycetota, and Bacteroidota constituted the dominant in AE, whereas Pseudomonadota, Actinomycetota, Bacteroidota, and Chloroflexota constituted the dominant in AT. Biomarkers were identified through LEFSe analysis, showing host-specific patterns. PCoA indicated distinct bacterial community structures. Phylogenetic analysis revealed diverse endophytic bacteria, including potential novel taxa. PICRUSt2 predicted diverse functions for endophytic bacteria in halophytes, indicating recruitment of beneficial bacterial taxa to adapt to extreme hypersaline conditions, including plant growth-promoting, biocontrol, and halophilic/tolerant bacteria. Moreover, the evolutionary relationship, metabolic capabilities, and plant beneficial potentials of the Bacillus swezeyi strains, previously isolated from the above two halophytes, were analyzed using comparative genomic and physiological analysis. The B. swezeyi strains displayed versatile environmental adaptability, as shown by their ability to use a wide range of carbon sources and their salt tolerances. B. swezeyi possessed a wide range of enzymatic capabilities, including but not limited to proteases, cellulases, and chitinases. Comparative genomic analysis revealed that despite some variations, they shared genetic similarities and metabolic capabilities among the B. swezeyi strains. B. swezeyi strains also displayed outstanding plant-growth-promoting and antagonistic potentials, offering potential solutions to the global food crisis. This study enhances our understanding of microbial diversity in halophytes on saline-alkali land in the West Aral Sea, shedding light on the halophyte microbiome and its collaboration with hosts in highly hypersaline environments. This study also provides a scientific basis for developing high-quality microbial fertilizers and implementing sustainable agricultural practices.

The impact of tumor resection on survival and functional outcomes for patients with primary central nervous system lymphoma.

PURPOSE: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection. METHODS: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection. RESULTS: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3 cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective. CONCLUSIONS: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3 cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes.

Optimal liquid-based DNA preservation for DNA barcoding of field-collected fungal specimens.

Preserving fungal tissue DNA in the field is essential for molecular ecological research, enabling the study of fungal biodiversity and community dynamics. This study systematically compares two liquid-based preservation solutions, RNAlater and DESS, for their effectiveness in maintaining macrofungi DNA integrity during field collection and storage. The research encompasses both controlled experiments and real-world field collections. In the controlled experiments, two fungal species were preserved in RNAlater and DESS at different temperatures and durations. DNA extraction success rates were high, but DNA quality and quantity metrics exhibited variations across samples. However, both preservation solutions demonstrated their viability for preserving fungal DNA, with no significant differences between them. In the field-collected macrofungi experiment, 160 paired fungal specimens were preserved in RNAlater and DESS, respectively. Including a drying process to facilitate tissue lysis for DNA extraction significantly impacted the outcomes. RNAlater showed a higher success rate and better DNA quality and quantity compared to DESS. Statistical analysis, including paired and independent t-tests, confirmed significant differences in DNA quality and quantity between the two preservation methods for field-collected samples. This study evaluates RNAlater and DESS for preserving macrofungi DNA in field conditions. Both methods are effective, but RNAlater is superior when a drying step is included in DNA extraction. Researchers can choose based on their specific needs without compromising DNA integrity. These findings advance fungal molecular ecology and DNA preservation strategies in ecological and environmental studies.

Metabonomic analysis to identify exometabolome changes underlying antifungal and growth promotion mechanisms of endophytic Actinobacterium Streptomyces albidoflavus for sustainable agriculture practice.

In recent years, there has been an increasing focus on microbial ecology and its possible impact on agricultural production, owing to its eco-friendly nature and sustainable use. The current study employs metabolomics technologies and bioinformatics approaches to identify changes in the exometabolome of Streptomyces albidoflavus B24. This research aims to shed light on the mechanisms and metabolites responsible for the antifungal and growth promotion strategies, with potential applications in sustainable agriculture. Metabolomic analysis was conducted using Q Exactive UPLC-MS/MS. Our findings indicate that a total of 3,840 metabolites were identified, with 137 metabolites exhibiting significant differences divided into 61 up and 75 downregulated metabolites based on VIP >1, |FC| >1, and p < 0.01. The interaction of S. albidoflavus B24 monoculture with the co-culture demonstrated a stronger correlation coefficient. The Principal Component Analysis (PCA) demonstrates that PCA1 accounted for 23.36%, while PCA2 accounted for 20.28% distinction. OPLS-DA score plots indicate significant separation among different groups representing (t1) 24% as the predicted component (to1) depicts 14% as the orthogonal component. According to the findings of this comprehensive study, crude extracts from S. albidoflavus demonstrated varying abilities to impede phytopathogen growth and enhance root and shoot length in tested plants. Through untargeted metabolomics, we discovered numerous potential molecules with antagonistic activity against fungal phytopathogens among the top 10 significant metabolites with the highest absolute log2FC values. These include Tetrangulol, 4-Hydroxybenzaldehyde, and Cyclohexane. Additionally, we identified plant growth-regulating metabolites such as N-Succinyl-L-glutamate, Nicotinic acid, L-Aspartate, and Indole-3-acetamide. The KEGG pathway analysis has highlighted these compounds as potential sources of antimicrobial properties. The inhibitory effect of S. albidoflavus crude extracts on pathogen growth is primarily attributed to the presence of specific gene clusters responsible for producing cyclic peptides such as ansamycins, porphyrin, alkaloid derivatives, and neomycin. Overall, it is apparent that crude extracts from S. albidoflavus exhibited varying abilities to inhibit the growth of three phytopathogens and enhancement in both root and shoot length of tested plants. This research enhances our understanding of how secondary metabolites contribute to growth promotion and biocontrol, supporting ecosystem sustainability and resilience while boosting productivity in sustainable agriculture.

Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish.

Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.

[Focal therapy for prostate cancer: Progress in research].

Prostate cancer (PCa) is currently the second most common malignancy in men worldwide，and its incidence rate is on the rise. Most cases of PCa are treated by radical prostatectomy, but with the development of medical imaging and innovation in therapeutic theories and technology, focal therapy has shown better application prospects in the treatment of PCa. Compared with radical prostatectomy, focal therapy yields satisfactory results in terms of effectiveness and reduction of complications in addition to avoidance of overtreatment and treatment-related financial burden. This article reviews the strategies of focal therapy for PCa, including cryoablation, high-intensity focused ultrasound, irreversible electroporation, and photodynamic therapy, with an analysis of the clinical trials in recent years.

[Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis].

The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.

Thermodynamically spontaneously intercalated H3O+ enables LiMn2O4 with enhanced proton tolerance in aqueous batteries.

LiMn2O4 (LMO) is an attractive positive electrode material for aqueous lithium-ion batteries (ALIBs), but its inferior cycle performance limits the practical application. The degradation mechanism of LMO in ALIBs is still unclear, resulting in inability to predictably improve its structural stability. The electrode/electrolyte interface is believed to play an important role in electrode degradation. However, the interactions of the water-containing electrode/electrolyte interface of LMO are underexplored. In this work, we demonstrate the insertion of H3O+ into LMO during cycling in aqueous electrolyte and elucidate the paradoxical effects of H3O+. The crystal H3O+ enhances the structural stability of LMO by forming a gradient Mn4+-rich protective shell, but an excess amount of crystal H3O+ leads to poor Li+ conductivity, resulting in rapid capacity fading. Combining electrochemical analyses, structural characterizations, and first-principles calculations, we reveal the intercalation of H3O+ into LMO and its associated mechanism on the structural evolution of LMO. Furthermore, we regulate the crystal H3O+ content in LMO by modifying the hydrogen bond networks of aqueous electrolyte to restrict H2O molecule activity. This approach utilizes an appropriate amount of crystal H3O+ to enhance the structural stability of LMO while maintaining sufficient Li+ diffusion.

Spatial evolution, influencing factors and spillover effects of logistics resilience in the Yangtze River Economic Belt.

Logistics resilience is a significant representation of sustainable development ability and a necessary support for high-quality economic development. In order to explore the influencing factors and realization mechanism of the improvement of logistics resilience of the Yangtze River Economic Belt and the high-quality and sustainable development of the economy, this paper comprehensively considers factors of the supply and demand relationship of the logistics market, industrial structure and ecological environment, and evaluates the urban logistics resilience of the Yangtze River Economic Belt by using POI data and statistical data. Combined with the spatial Durbin model, the influencing factors and spatial spillover effects of inter-city logistics resilience were revealed. This study found that the urban logistics resilience in the lower reaches of the Yangtze River has been high. Except Chongqing and Shanghai, the COVID-19 epidemic happened in 2020 led to a significant decrease in logistics resilience. In the meanwhile, every 1% increase in the logistics resilience of the city will promote the logistics resilience of the adjacent cities by 0.145%. Economic condition and urban development potential have positive effects on logistics resilience of the city and its adjacent cities. The economic condition has a direct effect coefficient of 0.166 and an indirect effect coefficient of 0.181, The direct and indirect effects of urban development potential are significantly positive, and the coefficients are 0.001 and 0.006, respectively. The level of information, government support and ability of technological innovation are helpful for the improvement of urban logistics resilience while hindering the enhancement of logistics resilience in adjacent cities. The research area can be extended in the future and more influencing factors can be considered in the future.

Alcohol-gating femtosecond laser-induced micro/nano-structured membranes with reversible switching wettability and breathability.

A reversible liquid gating membrane with the ability to regulate gas/liquid transport is critical for many fields, such as biological applications, multiphase separation, and sewerage treatment. Numerous membranes can respond to external stimuli and dynamically control gas/liquid fluid transport; however, simultaneously achieving regulated gas/liquid transport membranes through simple manufacturing remains a challenge. In this work, we investigated an alcohol-regulation gating membrane via femtosecond laser one-step processing, allowing in situ dynamically controllable gas/liquid transfer. More specifically, the porous membrane, processed by laser, exhibits excellent superhydrophobicity (WCA ∼ 153.4°) and breathability (water-vapor evaporation rates ∼118.3 mg (cm2 h)-1), enabling gas to penetrate but not water. In contrast, it allows the passage of water while preventing the permeation of gas subsequent to the introduction of alcohol. Furthermore, the porous membrane still possesses superbly consistent performance after being placed in air for 90 days or over 100 dropping-drying ethanol cycles test, indicating outstanding durability and reversibility. Significantly, the porous membrane has broad potential applications in medical dressings, providing a new strategy to fabricate next-generation bandages.

A brain cell atlas integrating single-cell transcriptomes across human brain regions.

While single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity. Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.3 million cells or nuclei from both healthy and diseased tissues. Using machine-learning based algorithms, the Brain Cell Atlas provides a consensus cell type annotation, and it showcases the identification of putative neural progenitor cells and a cell subpopulation of PCDH9high microglia in the human brain. We demonstrate the gene regulatory difference of PCDH9high microglia between hippocampus and prefrontal cortex and elucidate the cell-cell communication network. The Brain Cell Atlas presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.

Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis.

Parallel artificial membrane permeability analysis (PAMPA) is used to determine the permeability of compounds through concentrated negatively charged phospholipid bilayer barriers. We employed MacroFlux (a scaled-up version of PAMPA) to test the permeation rate of terazosin hydrochloride (TH) tablets and predict in vivo bioequivalence. The dissolution profiles and permeability of one reference formulation, and seven generic TH tablets, were compared. The dissolution profiles of these generic tablets were equivalent to that of the reference drug in four different media. However, the flux and the total permeated amount of some generic TH tablets were below the lower limit of the confidence interval of the original acceptance range in MacroFlux, which implied risk in the bioequivalence test in vivo. We further evaluated potential factors responsible for this discrepancy by µFlux, including active pharmaceutical ingredient (API) permeability and excipient prescriptions. The analysis showed that different properties of API were a main factor leading to biological inequivalence in the MacroFlux assay, while excipient prescriptions did not have an impact on bioequivalence risk. These data indicated that the flux assay may be a helpful as an auxiliary method for predicting bioequivalence of generic drugs and analyze the factors responsible for bioequivalence risk.

Continuous Dictionary of Nodes Model and Bilinear-Diffusion Representation Learning for Brain Disease Analysis.

Brain networks based on functional magnetic resonance imaging (fMRI) provide a crucial perspective for diagnosing brain diseases. Representation learning has recently attracted tremendous attention due to its strong representation capability, which can be naturally applied to brain disease analysis. However, traditional representation learning only considers direct and local node interactions in original brain networks, posing challenges in constructing higher-order brain networks to represent indirect and extensive node interactions. To address this problem, we propose the Continuous Dictionary of Nodes model and Bilinear-Diffusion (CDON-BD) network for brain disease analysis. The CDON model is innovatively used to learn the original brain network, with its encoder weights directly regarded as latent features. To fully integrate latent features, we further utilize Bilinear Pooling to construct higher-order brain networks. The Diffusion Module is designed to capture extensive node interactions in higher-order brain networks. Compared to state-of-the-art methods, CDON-BD demonstrates competitive classification performance on two real datasets. Moreover, the higher-order representations learned by our method reveal brain regions relevant to the diseases, contributing to a better understanding of the pathology of brain diseases.

The output of cataract surgery performed by trained non-ophthalmologist physicians in rural areas: study of cataract outcomes and up-take of services report 7.

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.

Stereochemical Control of Redox CoII/CoIII-Cages with Switchable Cotton Effects Based on Labile-Static States.

The structural dynamics of artificial assemblies, in aspects such as molecular recognition and structural transformation, provide us with a blueprint to achieve bioinspired applications. Here, we describe the assembly of redox-switchable chiral metal-organic cages Λ8/Δ8-[Pd6(CoIIL3)8]28+ and Λ8/Δ8-[Pd6(CoIIIL3)8]36+. These isomeric cages demonstrate an on-off chirality logic gate controlled by their chemical and stereostructural dynamics tunable through redox transitions between the labile CoII-state and static CoIII-state with a distinct Cotton effect. The transition between different states is enabled by a reversible redox process and chiral recognition originating in the tris-chelate Co-centers. All cages in two states are thoroughly characterized by NMR, ESI-MS, CV, CD, and X-ray crystallographic analysis, which clarify their redox-switching behaviors upon chemical reduction/oxidation. The stereochemical lability of the CoII-center endows the Λ8/Δ8-CoII-cages with efficient chiral-induction by enantiomeric guests, leading to enantiomeric isomerization to switch between Λ8/Δ8-CoII-cages, which can be stabilized by oxidation to their chemically inert forms of Λ8/Δ8-CoIII-cages. Kinetic studies reveal that the isomerization rate of the Δ8-CoIII-cage is at least an order of magnitude slower than that of the Δ8-CoII-cage even at an elevated temperature, while its activation energy is 16 kcal mol-1 higher than that of the CoII-cage.

CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.

Multipocket Cage Enables the Binding of High-Order Bulky and Drug Guests Uncovered by MS Methodology.

Achieving high guest loading and multiguest-binding capacity holds crucial significance for advancement in separation, catalysis, and drug delivery with synthetic receptors; however, it remains a challenging bottleneck in characterization of high-stoichiometry guest-binding events. Herein, we describe a large-sized coordination cage (MOC-70-Zn8Pd6) possessing 12 peripheral pockets capable of accommodating multiple guests and a high-resolution electrospray ionization mass spectrometry (HR-ESI-MS)-based method to understand the solution host-guest chemistry. A diverse range of bulky guests, varying from drug molecules to rigid fullerenes as well as flexible host molecules of crown ethers and calixarenes, could be loaded into open pockets with high capacities. Notably, these hollow cage pockets provide multisites to capture different guests, showing heteroguest coloading behavior to capture binary, ternary, or even quaternary guests. Moreover, a pair of commercially applied drugs for the combination therapy of chronic lymphocytic leukemia (CLL) has been tested, highlighting its potential in multidrug delivery for combined treatment.

Dtx2 Deficiency Induces Ependymo-Radial Glial Cell Proliferation and Improves Spinal Cord Motor Function Recovery.

Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.