Mechanistic insights into zinc oxide nanoparticles induced embryotoxicity via H3K9me3 modulation.

The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health.

Rapid-Response Water-Shrink Films with High Output Work Density Based on Polyethylene Oxide and α-Cyclodextrin for Autonomous Wound Closure.

Conventional wound closure methods, including sutures and tissue adhesives, present significant challenges for self-care treatment, particularly in the context of bleeding wounds. Existing stimuli-responsive contractile materials designed for autonomous wound closure frequently lack sufficient output work density to generate the force needed to bring the wound edges into proximity or necessitate stimuli that are not compatible with the human body. Here, semi-transparent, flexible, and water-responsive shrinkable films, composed of poly(ethylene oxide) and α-cyclodextrin, are reported. These films exhibit remarkable stability under ambient conditions and demonstrate significant contraction (≈50%) within 6 s upon exposure to water, generating substantial contractile stress (up to 6 MPa) and output work density (≈1028 kJ m-3), which is 100 times larger than that of conventional hydrogel and 25 times larger than that of skeletal muscles. Remarkably, upon hydration, these films are capable of lifting objects 10 000 times their own weight. Leveraging this technology, water-shrink tapes, which, upon contact with water, effectively constrict human skin and autonomously close bleeding wounds in animal models within 10 seconds, are developed further. This work offers a novel approach to skin wound management, showing significant potential for emergency and self-care scenarios.

Human-Wildlife Conflict Mitigation Based on Damage, Distribution, and Activity: A Case Study of Wild Boar in Zhejiang, Eastern China.

Human-wildlife conflicts are becoming increasingly common worldwide and are a challenge to biodiversity management. Compared with compensatory management, which often focuses on solving emergency conflicts, mitigation management allows decision-makers to better understand where the damage is distributed, how the species are distributed and when the species conduct their activity. Here, we integrated data collected from 90 districts/counties' damage surveys and 1271 camera traps to understand the damage status, abundance, density and activity rhythms of wild boar (Sus scrofa) in Zhejiang, Eastern China, from January 2019 to August 2023. We found that (1) wild boar-human conflicts were mainly distributed in the northwest and southwest mountainous regions of Zhejiang Province; (2) the total abundance of wild boar was 115,156 ± 24,072 individuals, indicating a growing trend over the past decade and a higher density in the western and southern regions; (3) wild boar exhibited different activity patterns across different damage regions, and the periods around 7:00, 11:00 and 16:00 represented activity peaks for wild boar in seriously damaged regions. The damage distribution, density, distribution and activity rhythms provide specific priority regions and activity intensity peaks for conflict mitigation. We believe that these findings based on the damage, distribution and activity could provide a scientific basis for mitigation management at the county level and enrich the framework of human-wildlife conflict mitigation.

Conformal Neuromorphic Bioelectronics for Sense Digitalization.

Sense digitalization, the process of transforming sensory experiences into digital data, is an emerging research frontier that links the physical world with human perception and interaction. This field is largely inspired by the adaptability, fault tolerance, robustness, and energy efficiency inherent in biological senses, driving the development of numerous innovative digitalization techniques. Among these techniques, neuromorphic bioelectronics, characterized by biomimetic adaptability, stand out for their seamless bidirectional interactions with biological entities through stimulus-response and feedback loops, incorporating bio-neuromorphic intelligence for information exchange. This review illustrates recent progress in sensory digitalization, encompassing not only the digital representation of physical sensations such as touch, light, and temperature, correlating to tactile, visual, and thermal perceptions, but also the detection of biochemical stimuli such as gases, ions, and neurotransmitters, mirroring olfactory, gustatory, and neural processes. It thoroughly examines the material design, device manufacturing, and system integration, offering detailed insights. However, the field faces significant challenges, including the development of new device/system paradigms, forging genuine connections with biological systems, ensuring compatibility with the semiconductor industry, and overcoming the absence of standardization. Looking ahead, the ambition is to realize biocompatible neural prosthetics, exoskeletons, soft humanoid robots, and cybernetic devices that integrate smoothly with both biological tissues and artificial components, bridging the gap between organic and synthetic realms. This article is protected by copyright. All rights reserved.

PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/ß-catenin pathway.

Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.

Association between kidney stones and poor sleep factors in U.S. adults.

The purpose of our study is to examine the correlation between sleep factors and the prevalence of kidney stones in US adults. A total of 34,679 participants from the National Health and Nutrition Examination Survey 2007 to 2018 were included in the analyses. Sleep data collection included: presleep factors (difficulty falling asleep, sleep onset latency), intra-sleep factors (risk index of obstructive sleep apnea, restless leg syndrome, difficulty maintaining sleep), post-sleep factors (daytime sleepiness, non-restorative sleep), sleep schedule and duration, and sleep quality. Logistic regression models were used to analyze the correlation between sleep factors and the prevalence of kidney stones. Among the 34,679 participants, the overall incidence of kidney stones was 9.3%. The presence of presleep factors (difficulty falling asleep [odds ratios [OR], 1.680; 95% CI, 1.310-2.150], prolonged sleep onset latency [OR, 1.320; 95% CI, 1.020-1.700]), intra-sleep factors (higher risk index of obstructive sleep apnea [OR, 1.750; 95% CI, 1.500-2.050], restless leg syndrome [OR, 1.520; 95% CI, 1.150-1.990], difficulty maintaining sleep [OR, 1.430; 95% CI, 1.130-1.810]), post-sleep factors (daytime sleepiness [OR, 1.430; 95% CI, 1.220-1.680], non-restorative sleep [OR, 1.400; 95% CI, 1.110-1.760]), short sleep duration (OR, 1.190; 95% CI, 1.080-1.310), mediate sleep quality (OR, 1.140; 95% CI, 1.020-1.290), and poor sleep quality (OR, 1.500; 95% CI, 1.310-1.720) are linked to the occurrence of kidney stones. However, short sleep onset latency, bedtime and wake-up time were not significantly associated with the prevalence of kidney stones. These findings showed positive associations between higher kidney stone prevalence and poor sleep factors.

A novel plant type, leaf disease and severity identification framework using CNN and transformer with multi-label method.

The growth of plants is threatened by numerous diseases. Accurate and timely identification of these diseases is crucial to prevent disease spreading. Many deep learning-based methods have been proposed for identifying leaf diseases. However, these methods often combine plant, leaf disease, and severity into one category or treat them separately, resulting in a large number of categories or complex network structures. Given this, this paper proposes a novel leaf disease identification network (LDI-NET) using a multi-label method. It is quite special because it can identify plant type, leaf disease and severity simultaneously using a single straightforward branch model without increasing the number of categories and avoiding extra branches. It consists of three modules, i.e., a feature tokenizer module, a token encoder module and a multi-label decoder module. The LDI-NET works as follows: Firstly, the feature tokenizer module is designed to enhance the capability of extracting local and long-range global contextual features by leveraging the strengths of convolutional neural networks and transformers. Secondly, the token encoder module is utilized to obtain context-rich tokens that can establish relationships among the plant, leaf disease and severity. Thirdly, the multi-label decoder module combined with a residual structure is utilized to fuse shallow and deep contextual features for better utilization of different-level features. This allows the identification of plant type, leaf disease, and severity simultaneously. Experiments show that the proposed LDI-NET outperforms the prevalent methods using the publicly available AI challenger 2018 dataset.

Effects of topography and stand spatial structure on the diameter at breast height growth of major pioneer tree species of natural broad-leaved mixed forests in Zhejiang Province, China.

Based on the continuous inventory data of forest resources in Zhejiang Province in 2019 and 2021, we used statistical methods such as polynomial regression to analyze the impacts of topography and forest spatial structure on average annual diameter at breast height (DBH) growth of main pioneer tree species in natural broad-leaved mixed forests. The results showed that DBH of Schima superba, Quercus glauca, Quercus fabri, Lithocarpus glaber, Castanopsis eyrei, and Castanopsis sclerophylla were between 5-50.8, 5-41.5, 5-50.8, 5-43.9, 5-55.5, and 5-46.1 cm, respectively. We classified all the trees into three classes based on DBH: small (6-12 cm), medium (12-14 cm), and large (>26 cm). The average annual DBH growth of S. superba and Q. glauca was the highest on semi-shady slope and shady slope, with increases of 2.9%-15.7% and 1.1%-41.2%, respectively. The average annual DBH growth of large-diameter S. superba, L. glaber, C. eyrei and C. sclerophylla decreased with the increase of slope, with a maximum decrease of 27.0% for S. superba, with no significant difference among small- and medium-diameter trees as a whole. The slope position did not affect the annual DBH growth of small-diameter trees, while that of medium- and large-diameter S. superba, Q. glauca, and large-diameter Q. fabri, L. glaber decreased with the change of slope position from downhill, mesoslope, uphill to ridge, with a maximum decrease of 28.1% for L. glabe, and the major-diameter C. eyrei was on the contrary. Appropriate increase in the mingling was beneficial to the average annual DBH growth of medium- and large-diameter trees. Moderate mixing was suitable for S. superba, while low degree mixing and moderate mixing was suitable for Q. glauca, Q. fabri and L. glaber, and intensive mixing was suitable for C. eyrei and C. sclerophylla. No significant difference was observed for minor-diameter trees under the mingling. The neighborhood comparison only had a significant effect on the average annual DBH growth of large-diameter Q. glauca, Q. fabri, and L. glaber, which was significantly higher under subdominance-moderation than moderation-inferiority. The average annual DBH growth in the study area was mainly affected by aspect and mixing degree.

Multiscale Heterogeneities-Based Piezoresistive Interfaces with Ultralow Detection Limitation and Adaptively Switchable Pressure Detectability.

Mechanical compliance and electrical enhancement are crucial for pressure sensors to promote performances when perceiving external stimuli. Here we propose a bioinspired multiscale heterogeneity-based interface to adaptively regulate its structure layout and switch to desirable piezoresistive behaviors with ultralow detection limitation. In such a multiscale heterogeneities system, the micro-/nanoscale spiny Ag-MnO2 heterostructure contributes to an ultralow detection limitation of 0.008 Pa and can perceive minor pressure increments under preloads with high resolution (0.0083%). The macroscale heterogeneous orientation of the cellular backbone enables anisotropic deformation, allowing the sensor to switch to rational sensitivity and working range (e.g., 580 kPa-1 for 0-20 kPa/54 kPa-1 for 60-140 kPa) as required. The sensor's stepwise activation progresses from the micro-/nanoscale heterostructure to the macroscale heterogeneous orientation, which can adaptively match diverse sensing tasks in complex applications scenarios. This multiscale heterogeneous and switchable design holds immense potential in the development of intelligent electromechanical devices, including wearable sensors, soft robotics, and smart actuators.

A Retrospective Analysis of the Computed Tomography Findings and Diagnosis of 53 Cases of Elastofibroma in the Infrascapular Region.

OBJECTIVE: In this work, we have used histopathology as the gold standard for the diagnosis, calculated the sensitivity and positive predictive value (PPV) of computed tomography (CT), and analyzed the CT and clinical characteristics of pathologically proven elastofibromas. METHODS: A systematic retrospective analysis was performed on all patients with infrascapular lesions who were treated in the hospital from 2006 to 2018. CT and histopathological examinations were performed for all cases, and the CT sensitivity and PPV for the diagnosis of elastofibroma were calculated. 12 of 53 cases (20 lesions) underwent enhanced CT scan after CT plain scan, and the related clinical and CT features of elastofibromas have been discussed. RESULTS: Of the 54 patients treated during the study, CT diagnosis was consistent with histopathology in 53 cases. One was a false-positive patient. The PPV and sensitivity of the CT in the diagnosis of elastofibroma were 93.3% (95% CI 68.0%-99.8%) and 100%, respectively. The CT values of 12 patients with 20 lesions on plain and enhanced scans were statistically significant (P=0.001). The prevalence of elastofibromas in males and females was statistically significant (P=.000). There was no statistically significant difference in the incidence of left and right elastofibromas (P=0.752). There was no significant difference in the volume of left and right lesions (P=0.209) and the volume of elastofibromas between males and females (P=.474). CONCLUSION: CT is the most practical tool for the evaluation of elastofibromas in the infrascapular region.

Pharmaceutical Manipulation of Mitochondrial F0F1-ATP Synthase Enables Imaging and Protection of Myocardial Ischemia/Reperfusion Injury Through Stress-induced Selective Enrichment.

To rescue ischemic myocardium from progressing to myocardial infarction, timely identification of the infarct size and reperfusion is crucial. However, fast and accurate identification, as well as the targeted protection of injured cardiomyocytes following ischemia/reperfusion (I/R) injury, remain significantly challenging. Here, a near infrared heptamethine dye IR-780 is shown that has the potential to quickly monitor the area at risk following I/R injury by selectively entering the cardiomyocytes of the at-risk heart tissues. Preconditioning with IR-780 or timely IR-780 administration before reperfusion significantly protects the heart from ischemia and oxidative stress-induced cell death, myocardial remodeling, and heart failure in both rat and pig models. Furthermore, IR-780 can directly bind to F0F1-ATP synthase of cardiomyocytes, rapidly decrease the mitochondrial membrane potential, and subsequently slow down the mitochondrial energy metabolism, which induces the mitochondria into a "quiescent state" and results in mitochondrial permeability transition pore inhibition by preventing mitochondrial calcium overload. Collectively, the findings show the feasibility of IR-780-based imaging and protection strategy for I/R injury in a preclinical context and indicate that moderate mitochondrial function depression is a mode of action that can be targeted in the development of cardioprotective reagents.

Sugarcane/soybean intercropping with reduced nitrogen addition promotes photosynthesized carbon sequestration in the soil.

Introduction: Sugarcane/soybean intercropping with reduced nitrogen (N) addition has improved soil fertility and sustainable agricultural development in China. However, the effects of intercropping pattern and N fertilizer addition on the allocation of photosynthesized carbon (C) in plant-soil system were far less understood. Methods: In this study, we performed an 13CO2 pulse labeling experiment to trace C footprints in plant-soil system under different cropping patterns [sugarcane monoculture (MS), sugarcane/soybean intercropping (SB)] and N addition levels [reduced N addition (N1) and conventional N addition (N2)]. Results and discussion: Our results showed that compared to sugarcane monoculture, sugarcane/soybean intercropping with N reduced addition increased sugarcane biomass and root/shoot ratio, which in turn led to 23.48% increase in total root biomass. The higher root biomass facilitated the flow of shoot fixed 13C to the soil in the form of rhizodeposits. More than 40% of the retained 13C in the soil was incorporated into the labile C pool [microbial biomass C (MBC) and dissolved organic C (DOC)] on day 1 after labeling. On day 27 after labeling, sugarcane/soybean intercropping with N reduced addition showed the highest 13C content in the MBC as well as in the soil, 1.89 and 1.14 times higher than the sugarcane monoculture, respectively. Moreover, intercropping pattern increased the content of labile C and labile N (alkaline N, ammonium N and nitrate N) in the soil. The structural equation model indicated that the cropping pattern regulated 13C sequestration in the soil mainly by driving changes in labile C, labile N content and root biomass in the soil. Our findings demonstrate that sugarcane/soybean intercropping with reduced N addition increases photosynthesized C sequestration in the soil, enhances the C sink capacity of agroecosystems.

Physiological responses of typical subtropical landscape shrubs to artificial light at night.

Artificial light at night is rapidly spreading and has become an important component of global change. Although numerous studies have focused on its potential ecological impacts, the physiological response mechanisms of landscape plants to artificial light at night have rarely been quantified. With common landscape shrubs in subtropical regions of China, Hydrangea paniculata, Photinia fraseri and Ligustrum japonicum, as test materials, we exa-mined the responses of antioxidant enzyme system and biomass in the light environment at night under different light quality (yellow light, white light) with different light intensities (20, 40, 60 lx) . The results showed that artificial light at night significantly increased the membrane peroxidation, stimulated plant antioxidant protection systems and raised the antioxidant enzyme activities of the three species. The effects of light quality on plant antioxidant enzymes varied across dspecies. The peroxidase (POD) and catalase (CAT) activities of H. paniculata under white light were 1.5 and 1.3 times as that under yellow light, respectively. Both enzyme activities of P. fraseri were 1.1 times as that under white light than under yellow light. The activities of two enzymes in L. japonicum under white light were 88.6% and 99.5% of those under yellow light, respectively. The antioxidant enzyme activities of the three species increased with increasing light intensity at night, whereas the contents of malondialdehyde increased rapidly and the antioxidant enzyme activities decreased when beyond a certain light intensity threshold (at 120 d, the threshold was about 40 lx). The protective enzymes that played the major role under nighttime light stress were different among the three species. For H. paniculata, POD and CAT complemented each other to resist stress-induced oxidative damage, while the main enzyme of L. japonicum was POD. The biomass of the three species increased significantly under artificial light at night. H. paniculata was the most sensitive to nighttime light stress, while L. japonicum had the strongest resistance to the stress. The deciduous shrub H. paniculata could tolerate the white night light lower than 40 lx, while the evergreen shrubs P. fraseri and L. japonicum could tolerate the yellow night light lower than 40 lx.

Hyaluronic Acid-Conjugated Fluorescent Probe-Shielded Polydopamine Nanomedicines for Targeted Imaging and Chemotherapy of Bladder Cancer.

Bladder cancer is one of the most common malignancies in the urinary system, with high risk of recurrence and progression. However, the difficulty in detecting small tumor lesions and the lack of selectivity of intravesical treatment seriously affect the prognosis of patients with bladder cancer. In the present work, a nanoparticle-based delivery system with tumor targeting, high biocompatibility, simple preparation, and the ability to synergize imaging and therapy was fabricated. Specifically, this nanosystem consisted of the core of doxorubicin (DOX)-loaded polydopamine nanoparticles (PDD NPs) and the shell of hyaluronic acid (HA)-conjugated IR780 (HA-IR780). The HA-IR780-covered PDD NPs (HR-PDD NPs) demonstrated tumor targeting and visualization both in vitro and in vivo with properties of promoted cancer cell endocytosis and lysosomal escape, efficiently delivering drugs to the target site and exerting a killing effect on tumor cells. Encouragingly, intravesical instillation of HR-PDD NPs improved drug retention in the bladder and promoted its accumulation in tumor tissue, resulting in better tumor proliferation inhibition and apoptosis in an orthotopic bladder cancer model in rats. This study provides a promising strategy for the diagnosis and therapy of bladder cancer.

Characterization of the complete chloroplast genome of Firmiana hainanensis (Malvaceae), an endemic and vulnerable tree species of China.

Firmiana hainanensis Kosterm. is a commercially valuable endemic tree species in China and has long been considered a globally vulnerable species. We assembled and characterized the complete chloroplast genome of this species by using Illumina pair-end sequencing data. The total chloroplast genome size was 161,559 bp, including two inverted repeats (IRs) of 25,612 bp, separated by a large single copy (LSC) and a small single copy (SSC) regions of 90,057 and 20,277 bp, respectively. A total of 130 genes were identified, including 85 protein-coding genes, 37 tRNA, and eight rRNA genes. Phylogenetic analysis showed that F. hainanensis was the most basal species in the genus Firmiana. The chloroplast genome of this species will provide a theoretical basis to understand the taxa's evolution further and is expected to contribute to its conservation efforts.

Characterization of the complete chloroplast genome of Trailliaedoxa gracilis (Rubiaceae).

Trailliaedoxa gracilis (Rubiaceae) is a Chinese endemic monotypic genus distributed in southwestern China. This study reported the complete chloroplast genome of T. gracilis assembled from Illumina sequencing reads. The chloroplast genome size is 152,407 bp, containing a single large copy (LSC) region of 82,957 bp, a short single copy (SSC) region of 17,936 bp, and a pair of inverted repeats (IRs) of 25,757 bp. A total of 127 genes were found, including 82 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A phylogenetic analysis using the maximum likelihood algorithm revealed that T. gracilis belonged to the subfamily Ixoroideae and had the closest relationship with Scyphiphora hydrophyllacea.

Intravesical IR-780 instillation prevents radiation cystitis by protecting urothelial integrity.

PURPOSE: To explore an efficient preventive strategy for radiation cystitis. METHODS: We instilled IR-780 into the bladders of rats 1 h before bladder irradiation, and its bio-distribution was observed at different times. Bladders were then examined for pathogenic alterations and inflammation levels by day 3 and week 12 postirradiation, and the functional characteristics of the bladder were tested via cystometry by week 12. Human uroepithelial sv-huc-1 cells were used to determine the effect of IR-780 on cell viability, regardless of irradiation. We measured the intracellular levels of oxidative stress, DNA damage, apoptosis proportion, and the expression of antioxidant proteases and apoptotic caspases in IR-780 pretreated cells after radiation. RESULTS: IR-780 is localized in the urothelium after intravesical instillation in vivo. Ionizing radiation could induce acute impairment of the bladder urothelium and inflammation in the bladder on day 3. Fibrosis of the irradiated bladder progressed and eventually affected voiding function at 12 weeks. Treatment with IR-780 before irradiation ameliorated these changes. In vitro, IR-780 protected against cell viability and apoptosis of sv-huc-1 cells after irradiation. Additionally, IR-780 may assist in eliminating reactive oxygen species and repairing irradiation-induced DNA damage. CONCLUSION: Our data indicate that IR-780 can be used before irradiation to prevent acute urinary mucosal injury and late bladder dysfunction. Moreover, early urothelial impairment plays a significant role in radiation cystitis development.

Hyperbaric oxygen enhanced the chemotherapy of mitochondrial targeting molecule IR-780 in bladder cancer.

BACKGROUND: Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. MATERIAL AND METHODS: The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. RESULTS: IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. CONCLUSION: We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

Astrocytic connexin 43 deletion ameliorates SNI-induced neuropathic pain by reducing microglia activation.

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP. In the present study, we found that Cx43 deletion significantly ameliorated spared nerve injury (SNI)-induced NP and suppressed SNI induced c-Fos expression in the spinal cord. Notably, Cx43 deletion led to much less SNI-induced microglia activation in the spinal cord. These results suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP.