The pressing need to address the global water crisis has spurred research efforts toward exploring alternative sources and technologies, and harvesting atmospheric water from the humid air emerges as a promising solution. Liquid desiccants, known for their high absorption capacity, have been widely utilized for moisture capture, but their water yield is mainly restricted by sluggish adsorption and desorption dynamics. To address this limitation, we present a facile strategy to promote the absorption/desorption dynamics of moisture by virtue of capillary transport and enlarged interfaces in a photothermal wood enhancer. These enhancers are fabricated via partial delignification of natural balsa woods followed by low-temperature carbonization to endow them with photo-thermal properties. The moisture absorption rate shows a notable increase of 103% and 84% under the relative humidity (RH) of 60% and 90%, respectively, within the initial two hours by applying the three enhancers. On the other hand, the desorption efficiency is doubled, reaching 80% in two hours under 60 • C with the enhancers. Moreover, the desorption can be driven by solar energy with an evaporation rate of 1.217 kg⋅m − 2 ⋅h − 1. This work provides a design strategy combining capillary and interfacial effects to enhance moisture harvesting without altering hygroscopic materials.
Maxillofacial bone defects caused by congenital malformations, trauma, tumors, and inflammation can severely affect functions and aesthetics of maxillofacial region. Despite certain successful clinical applications of biomaterial scaffolds, ideal bone regeneration remains a challenge in maxillofacial region due to its irregular shape, complex structure, and unique biological functions. Scaffolds that address multiple needs of maxillofacial bone regeneration are under development to optimize bone regeneration capacity, costs, operational convenience. etc. In this review, we first highlight the special considerations of bone regeneration in maxillofacial region and provide an overview of the biomaterial scaffolds for maxillofacial bone regeneration under clinical examination and their efficacy, which provide basis and directions for future scaffold design. Latest advances of these scaffolds are then discussed, as well as future perspectives and challenges. Deepening our understanding of these scaffolds will help foster better innovations to improve the outcome of maxillofacial bone tissue engineering.
Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane and DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects and impacts mitochondrial dynamics. Herein, to study the detailed dynamics of mitochondrial membrane and mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, that could be used for simultaneously monitoring mitochondrial membrane and mtDNA dynamics via separate color outputs. By combining mtGLP with structured illumination microscopy to monitor mitochondrial dynamics, we discover the formation of nucleoid condensates in damaged mitochondria. We further reveal that nucleoid condensates promoted the peripheral fission of damaged mitochondria via asymmetric segregation. Through simulations, we find that the peripheral fission events occurred when the nucleoid condensates interacted with the highly curved membrane regions at the two ends of the mitochondria. Overall, we show that mitochondrial nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis.
Macrophage-mediated inflammation plays a significant role in the development and progression of diabetic kidney disease (DKD). Studies have suggested that impaired macrophage efferocytosis aggravates the inflammatory response. However, its contribution to DKD progression remains unknown. Using single-cell RNA sequencing (scRNA-seq) data obtained from the GSE131882, GSE195460, GSE151302, GSE195460, and GSE131685 datasets, we successfully clustered 13 cell types. Through analysis of the ligand-receptor network, it was discovered that macrophages interact with other cells. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that macrophages exhibit a heightened presence of phagocytosis signaling. We discovered that RAC1 was closely related to macrophage efferocytosis through a Venn diagram and protein-protein interaction (PPI) analysis, which predicted the correlation with the clinical features of DKD using the NephroseqV5 tool. Furthermore, we verified that RAC1 exhibited decreased expression in macrophages cultured with lipopolysaccharide (LPS) and high glucose. Nevertheless, the overexpression of RAC1 promoted macrophage efferocytosis and inhibited the inflammatory response. In summary, our study focused on examining the presence and importance of efferocytosis-related molecules in DKD macrophages. Through a comprehensive analysis using scRNA-seq, we discovered that RAC1 plays a crucial role as an efferocytosis molecule in DKD. These findings enhance our current knowledge of the molecular mechanisms involved in the development of DKD and aid the exploration of new treatments.
Implanted neural electrodes have been widely used to treat brain diseases that require high sensitivity and biocompatibility at the tissue‐electrode interface. However, currently used clinical electrodes cannot meet both these requirements simultaneously, which hinders the effective recording of electronic signals. Herein, nanozyme‐based neural electrodes incorporating bioinspired atomically precise clusters were developed as a general strategy with a heterogeneous design for multiscale and ultrasensitive neural recording via quantum transport and biocatalytic processes. Owing to the dual high‐speed electronic and ionic currents at the electrode‐tissue interface, the impedance of nanozyme electrodes was 26 times lower than that of state‐of‐the‐art metal electrodes, and the acquisition sensitivity for the local field potential was ∼10 times higher than that of clinical PtIr electrodes, enabling a signal‐to‐noise ratio (SNR) of up to 14.7 dB for single‐neuron recordings in rats. The electrodes provided more than 100‐fold higher antioxidant and multi‐enzyme‐like activities, which effectively decreased 67% of the neuronal injury area by inhibiting glial proliferation and allowing sensitive and stable neural recording. Moreover, nanozyme electrodes can considerably improve the SNR of seizures in acute epileptic rats and is expected to achieve precise localization of seizure foci in clinical settings. This article is protected by copyright. All rights reserved
Mesenchymal stem cells (MSCs) have become a promising therapeutic method. More safety data are needed to support clinical studies in more diseases. The aim of this study was to investigate the short- and long-term safety of human bone marrow–derived MSCs (hBMMSCs) in mice. In the present study, we injected control (saline infusion only), low (1.0 × 10⁶/kg), medium (1.0 × 10⁷/kg), and high (1.0 × 10⁸/kg) concentrations of hBMMSCs into BALB/c mice. The safety of the treatment was evaluated by observing changes in the general condition, hematology, biochemical indices, pathology of vital organs, lymphocyte subsets, and immune factor levels on days 14 and 150. In the short-term toxicity test, no significant abnormalities were observed in the hematological and biochemical parameters between the groups injected with hBMMSCs, and no significant damage was observed in the major organs, such as the liver and lung. In addition, no significant differences were observed in the toxicity-related parameters among the groups in the long-term toxicity test. Our study also demonstrates that mice infused with different doses of hBMMSCs do not show abnormal immune responses in either short-term or long-term experiments. We confirmed that hBMMSCs are safe through a 150-day study, demonstrating that this is a safe and promising therapy and offering preliminary safety evidence to promote future clinical applications of hBMMSCs in different diseases.
Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
Radiotherapy for head and neck tumors can lead to a severe complication known as radiation-induced brain injury (RIBI). However, the underlying mechanism of RIBI development remains unclear, and limited prevention and treatment options are available. Neuroactive steroids have shown potential in treating neurological disorders. 5α-Androst-3β, 5, 6β-triol (TRIOL), a synthetic neuroprotective steroid, holds promise as a treatment candidate for RIBI patients. However, the neuroprotective effects and underlying mechanism of TRIOL on RIBI treatment are yet to be elucidated. In the present study, our findings demonstrate TRIOL’s potential as a neuroprotective agent against RIBI. In gamma knife irradiation mouse model, TRIOL treatment significantly reduced brain necrosis volume, microglial activation, and neuronal loss. RNA-sequencing, immunofluorescence, real-time quantitative polymerase chain reaction, siRNA transfection, and western blotting techniques revealed that TRIOL effectively decreased microglial activation, proinflammatory cytokine release, neuron loss, and guanylate-binding protein 5 (GBP5) expression, along with its downstream signaling pathways NF-κB and NLRP3 activation in vitro. In summary, TRIOL effectively alleviate RIBI by inhibiting the GBP5/NF-κB/NLRP3 signal axis, reducing microglia activation and pro-inflammation cytokines release, rescuing neuron loss. This study highlights the potential of TRIOL as a novel and promising therapy drug for RIBI treatment. Graphical Abstract
Objective: Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression; however, the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive. It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets. Methods: We employed high-throughput sequencing-based high-throughput screening (HTS 2) to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators. Then, bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer. Results: Utilizing these gene expression signatures, we classified the epigenetic regulators into five distinct clusters, each characterized by specific functions. We discovered functional similarities between BAZ2B and SETMAR, as well as CLOCK and CBX3. Moreover, we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation. Notably, we constructed an epigenetic regulatory network based on the gene expression signatures, which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer. Conclusions: Our work deciphered the extensive regulation among hundreds of epigenetic regulators. The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.
Purpose Dysfunctions of retinal pigment epithelium (RPE) attributed to oxidative stress and inflammation are implicated with age-related macular degeneration (AMD). A debate on the curative role of metformin in AMD has been raised, though several recent clinical studies support the lower odds by using metformin. This study aimed to determine whether metformin could exert cytoprotection against RPE oxidative damages and the potential mechanisms. Methods A cellular AMD model was established by treating ARPE-19 cells with hydrogen peroxide (H2O2) for 24 h. The reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and levels of pro-inflammatory cytokines were monitored under administrations with H2O2 with/without metformin. The expression and DNA-binding activity of transcription factor erythroid-related factor 2 (Nrf2) were determined by western blot, immunofluorescence, and electrophoretic mobility shift assay. Knockout of Nrf2 was conducted by CRISPR/Cas9 gene deletion system. Results Metformin pretreatment significantly improved the H2O2-induced low viability of ARPE-19 cells, reduced ROS production, and increased contents of antioxidative molecules. Concurrently, metformin also suppressed levels of pro-inflammatory cytokines caused by H2O2. The metformin-augmented nuclear translocation and DNA-binding activity of Nrf2 were further verified by the increased expression of its downstream targets. Genetic deletion of Nrf2 blocked the cytoprotective role of metformin. Conclusion Metformin possesses antioxidative and anti-inflammatory properties in ARPE-19 cells by activating the Nrf2 signaling. It supports the potential use for the control and prevention of AMD.
Agrobiodiversity plays a crucial role in maintaining sustainable agricultural systems and supporting local livelihoods, but its integration into indigenous social institutions and cultures remains under-researched. We used a qualitative approach entailing in-depth interviews and participant observation to conduct research among the Rukai indigenous farmers in Taiwan focusing on: (1) how Rukai farmers practice agrobiodiversity, and (2) how these agricultural practices integrated into social institutions and cultural norms. Our findings reveal that food security and risk minimization are the prime considerations to preserve agrobiodiversity. Rukai farmers practice swidden cultivation utilizing five mixed cropping systems in seven different ecosystems that vary by elevation, length of exposure to sunlight, and temperature, intercropping, and regular fallows to maintain soil fertility. Importantly, Rukai agricultural practices are integrated into four social institutions that regulate the distribution and management of land and resources, the timing and nature of agricultural activities, and social recognition and status to ensure maximum production throughout the year and reducing risks posed by climate change.
Background The role of cholesterol metabolism in gastric cancer (GC) and its implications for tumor characteristics and immunotherapy response remain poorly understood. In this study, our aim was to investigate this role, identify associated metabolic subtypes, and assess their clinical implications in GC. Methods We conducted a comprehensive analysis of cholesterol metabolism genes (CMGs) using transcriptomic data from TCGA and GEO. Based on 23 representative CMGs, we classified GC into metabolic subtypes. We evaluated clinical features and immune cell infiltration between these subtypes. Additionally, we identified a CMG signature and assessed its clinical relevance in GC. We retrospectively enrolled thirty-five GC patients receiving chemotherapy plus a PD-1 inhibitor to assess the CMG signature using multiplex immunohistochemistry. Results Our analysis revealed two cholesterol metabolism subtypes in GC: Cholesterol Metabolism Type 1 (CMT1) and Cholesterol Metabolism Type 2 (CMT2). These subtypes exhibited distinct patterns: CMT1 indicated heightened cholesterol biosynthesis, while CMT2 showed abnormal cholesterol transport. CMT2 was associated with unfavorable clinical features, enriched malignant pathways, and a pro-tumor immune microenvironment. Furthermore, we developed a five-CMG prognostic signature (ABCA1, NR1H3, TSPO, NCEH1, and HMGCR) that effectively predicted the prognosis of patients with GC and their response to chemotherapy plus a PD-1 inhibitor. This signature was validated in a clinical cohort using multiplex immunohistochemistry. Conclusion Our results highlight the effectiveness of cholesterol metabolism patterns as biomarkers for predicting the prognosis and immunotherapy response in GC. The expression of cholesterol metabolism genes and the assessment of cholesterol metabolism patterns have the potential to predict the outcome of immunotherapy and guide treatment strategies.
GCLiPP is a global RNA interactome capture method that detects RNA-binding protein (RBP) occupancy transcriptome-wide. GCLiPP maps RBP-occupied sites at a higher resolution than phase separation-based techniques. GCLiPP sequence tags correspond with known RBP binding sites and are enriched for sites detected by RBP-specific crosslinking immunoprecipitation (CLIP) for abundant cytosolic RBPs. Comparison of human Jurkat T cells and mouse primary T cells uncovers shared peaks of GCLiPP signal across homologous regions of human and mouse 3′ UTRs, including a conserved mRNA-destabilizing cis-regulatory element. GCLiPP signal overlapping with immune-related SNPs uncovers stabilizing cis-regulatory regions in CD5, STAT6, and IKZF1.
Convolutional neural networks (CNNs) and self-attention (SA) have demonstrated remarkable success in low-level vision tasks, such as image super-resolution, deraining, and dehazing. The former excels in acquiring local connections with translation equivariance, while the latter is better at capturing long-range dependencies. However, both CNNs and Transformers suffer from individual limitations, such as limited receptive field and weak diversity representation of CNNs during low efficiency and weak local relation learning of SA. To this end, we propose a multi-scale fusion and decomposition network (MFDNet) for rain perturbation removal, which unifies the merits of these two architectures while maintaining both effectiveness and efficiency. To achieve the decomposition and association of rain and rain-free features, we introduce an asymmetrical scheme designed as a dual-path mutual representation network that enables iterative refinement. Additionally, we incorporate high-efficiency convolutions throughout the network and use resolution rescaling to balance computational complexity with performance. Comprehensive evaluations show that the proposed approach outperforms most of the latest SOTA deraining methods and is versatile and robust in various image restoration tasks, including underwater image enhancement, image dehazing, and low-light image enhancement. The source codes and pretrained models are available at https://github.com/qwangg/MFDNet.
Background The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. Objective This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. Methods Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. Results A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. Conclusions Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. Trial Registration Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882
Assimilation of sulfur is vital to all organisms. In S . cerevisiae , inorganic sulfate is first reduced to sulfide, which is then affixed to an organic carbon backbone by the Met17 enzyme. The resulting homocysteine can then be converted to all other essential organosulfurs such as methionine, cysteine, and glutathione. This pathway has been known for nearly half a century, and met17 mutants have long been classified as organosulfur auxotrophs, which are unable to grow on sulfate as their sole sulfur source. Surprisingly, we found that met17 Δ could grow on sulfate, albeit only at sufficiently high cell densities. We show that the accumulation of hydrogen sulfide gas underpins this density-dependent growth of met17 Δ on sulfate and that the locus YLL058W ( HSU1 ) enables met17 Δ cells to assimilate hydrogen sulfide. Hsu1 protein is induced during sulfur starvation and under exposure to high sulfide concentrations in wild-type cells, and the gene has a pleiotropic role in sulfur assimilation. In a mathematical model, the low efficiency of sulfide assimilation in met17 Δ can explain the observed density-dependent growth of met17 Δ on sulfate. Thus, having uncovered and explained the paradoxical growth of a commonly used “auxotroph,” our findings may impact the design of future studies in yeast genetics, metabolism, and volatile-mediated microbial interactions.
Importance Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results There were 437 539 484 (95% uncertainty interval [UI], 325 463 851-575 573 588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228 530 964; 95% UI, 172 515 833-297 118 596). Over 3 decades, visual impairment-associated DALYs increased from 7 601 852 (95% UI, 5 047 030-11 107 897) to 12 563 276 (95% UI, 8 278 866-18 961 723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100 000 population in 2019 (26 008.45; 95% UI, 19 987.35-32 482.09), while South Sudan had the highest DALY rate per 100 000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.
Plant diseases, which seriously damage crop production, are in most cases caused by fungal pathogens. In this study, we found that the Raf-like MAPKKKs STY8 (SERINE/THREONINE/TYROSINE KINASE 8), STY17, and STY46 negatively regulate resistance to the fungal pathogen Botrytis cinerea through jasmonate response in Arabidopsis. Moreover, STY8/STY17/STY46 homologs negatively contribute to chitin signaling. We further identified MKK7 as the MAPKK component interacting with STY8/STY17/STY46 homologs. MKK7 positively contributes to resistance to B. cinerea and chitin signaling. Furthermore, we found that STY8/STY17/STY46 homologs negatively affect the accumulation of MKK7, in accordance with the opposite roles of MKK7 and STY8/STY17/STY46 homologs in defense against B. cinerea. These results provide new insights into the mechanisms precisely regulating plant immunity via Raf-like MAPKKKs.
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