Unveiling the Potential of Ambient Air Annealing for Highly Efficient Inorganic CsPbI3 Perovskite Solar Cells.

Here, we report a detailed surface analysis of dry- and ambient air-annealed CsPbI3 films and their subsequent modified interfaces in perovskite solar cells. We revealed that annealing in ambient air does not adversely affect the optoelectronic properties of the semiconducting film; instead, ambient air-annealed samples undergo a surface modification, causing an enhancement of band bending, as determined by hard X-ray photoelectron spectroscopy measurements. We observe interface charge carrier dynamics changes, improving the charge carrier extraction in CsPbI3 perovskite solar cells. Optical spectroscopic measurements show that trap state density is decreased due to ambient air annealing. As a result, air-annealed CsPbI3-based n-i-p structure devices achieved a 19.8% power conversion efficiency with a 1.23 V open circuit voltage.

Rheb1 is required for limb growth through regulating chondrogenesis in growth plate.

Ras homology enriched in the brain (Rheb) is well established as a critical regulator of cell proliferation and differentiation in response to growth factors and nutrients. However, the role of Rheb1 in limb development remains unknown. Here, we found that Rheb1 was dynamically expressed during the proliferation and differentiation of chondrocytes in the growth plate. Given that Prrx1+ limb-bud-like mesenchymal cells are the source of limb chondrocytes and are essential for endochondral ossification, we conditionally deleted Rheb1 using Prrx1-Cre and found a limb dwarfism in Prrx1-Cre; Rheb1fl/fl mice. Normalized to growth plate height, the conditional knockout (cKO) mice exhibited a significant decrease in column count of proliferative zones which was increased in hypertrophic zones resulting in decreased growth plate size, indicating abnormal endochondral ossification. Interestingly, although Rheb1 deletion profoundly inhibited the transcription factor Sox9 in limb cartilage; levels of runx2 and collagen type 2 were both increased. These novel findings highlight the essential role of Rheb1 in limb growth and indicate a complex regulation of Rheb1 in chondrocyte proliferation and differentiation.

The toxicity response of the electrochemical signal of the cell to the drug metabolized by the S9 system.

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.

A Novel Frame-Selection Metric for Video Inpainting to Enhance Urban Feature Extraction.

In our digitally driven society, advances in software and hardware to capture video data allow extensive gathering and analysis of large datasets. This has stimulated interest in extracting information from video data, such as buildings and urban streets, to enhance understanding of the environment. Urban buildings and streets, as essential parts of cities, carry valuable information relevant to daily life. Extracting features from these elements and integrating them with technologies such as VR and AR can contribute to more intelligent and personalized urban public services. Despite its potential benefits, collecting videos of urban environments introduces challenges because of the presence of dynamic objects. The varying shape of the target building in each frame necessitates careful selection to ensure the extraction of quality features. To address this problem, we propose a novel evaluation metric that considers the video-inpainting-restoration quality and the relevance of the target object, considering minimizing areas with cars, maximizing areas with the target building, and minimizing overlapping areas. This metric extends existing video-inpainting-evaluation metrics by considering the relevance of the target object and interconnectivity between objects. We conducted experiment to validate the proposed metrics using real-world datasets from Japanese cities Sapporo and Yokohama. The experiment results demonstrate feasibility of selecting video frames conducive to building feature extraction.

Functional teeth and cognitive function among the Chinese elderly: The chain mediating effect of depressive symptoms and social participation.

The objective of this study was to investigate the chain mediating effects of depressive symptoms and social participation between functional teeth and cognitive function based on the biopsychosocial model. Data from the 2018 China Health and Retirement Longitudinal Study were analyzed. The findings revealed a favorable connection between the lack of edentulism and cognitive function, persisting even when accounting for the mediating factors of denture usage, depressive symptoms, and social participation. Furthermore, the study identified six indirect pathways in this relationship. The present study has substantiated the correlation between edentulism and cognitive function, thereby proposing that interventions aimed at denture usage, depressive symptoms, and social participation could potentially serve as preventive measures against cognitive decline in elderly individuals afflicted with edentulism. This underscores the significance of addressing these factors to alleviate cognitive decline.

Regularization Meets Enhanced Multi-Stage Fusion Features: Making CNN More Robust against White-Box Adversarial Attacks.

Regularization has become an important method in adversarial defense. However, the existing regularization-based defense methods do not discuss which features in convolutional neural networks (CNN) are more suitable for regularization. Thus, in this paper, we propose a multi-stage feature fusion network with a feature regularization operation, which is called Enhanced Multi-Stage Feature Fusion Network (EMSF2Net). EMSF2Net mainly combines three parts: multi-stage feature enhancement (MSFE), multi-stage feature fusion (MSF2), and regularization. Specifically, MSFE aims to obtain enhanced and expressive features in each stage by multiplying the features of each channel; MSF2 aims to fuse the enhanced features of different stages to further enrich the information of the feature, and the regularization part can regularize the fused and original features during the training process. EMSF2Net has proved that if the regularization term of the enhanced multi-stage feature is added, the adversarial robustness of CNN will be significantly improved. The experimental results on extensive white-box attacks on the CIFAR-10 dataset illustrate the robustness and effectiveness of the proposed method.

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

Stabilization of Highly Efficient and Stable Phase-Pure FAPbI3 Perovskite Solar Cells by Molecularly Tailored 2D-Overlayers.

As a result of their attractive optoelectronic properties, metal halide APbI3 perovskites employing formamidinium (FA+ ) as the A cation are the focus of research. The superior chemical and thermal stability of FA+ cations makes α-FAPbI3 more suitable for solar-cell applications than methylammonium lead iodide (MAPbI3 ). However, its spontaneous conversion into the yellow non-perovskite phase (δ-FAPbI3 ) under ambient conditions poses a serious challenge for practical applications. Herein, we report on the stabilization of the desired α-FAPbI3 perovskite phase by protecting it with a two-dimensional (2D) IBA2 FAPb2 I7 (IBA=iso-butylammonium overlayer, formed via stepwise annealing. The α-FAPbI3 /IBA2 FAPb2 I7 based perovskite solar cell (PSC) reached a high power conversion efficiency (PCE) of close to 23 %. In addition, it showed excellent operational stability, retaining around 85 % of its initial efficiency under severe combined heat and light stress, that is, simultaneous exposure with maximum power tracking to full simulated sunlight at 80 °C over 500 h.

Long Noncoding RNA COPDA1 Promotes Airway Smooth Muscle Cell Proliferation in Chronic Obstructive Pulmonary Disease.

Abnormal expression of long noncoding RNAs (lncRNAs) has been confirmed to be associated with many diseases, including chronic obstructive pulmonary disease (COPD). To gain better understanding of the mechanism of COPD, we investigated the lncRNA and mRNA profiles in the lung tissue of patients with COPD. According to the analysis, one of the significantly different lncRNAs, COPDA1, might participate in the occurrence and development of COPD. Lung tissues were collected from nonsmokers, smokers, or smokers with COPD for RNA sequencing. Bioinformatic analysis and cell experiments were used to define the function of COPDA1, and the effects of COPDA1 on intracellular Ca2+ concentration and cell proliferation were examined after knockdown or overexpression of COPDA1. A number of variations of lncRNAs were found in the comparison of nonsmokers, smokers, and smokers with COPD. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses indicated that smoking was involved in the activation of cytokines and the cell cycle, which is associated with COPD. According to the lncRNA-mRNA-coexpressing network and enrichment analysis, COPDAz1 and one of its target genes, MS4A1 (membrane-spanning 4-domains family, subfamily A) were investigated, and we discovered that the expression of MS4A1 was closely associated with lncRNA COPDA1 expression in human bronchial smooth muscle cells (HBSMCs). Further study showed that lncRNA COPDA1 upregulated the expression of MS4A1 to increase store-operated calcium entry in the HBSMCs, resulting in the promotion of the proliferation of smooth muscle cells as well as of airway remodeling. COPDA1 might be involved in the regulation of certain signaling pathways in COPD, might promote the proliferation of HBSMCs, and might also be involved in facilitating airway remodeling.

Correlation analysis of the transcriptome and metabolome reveals the regulatory network for lipid synthesis in developing Brassica napus embryos.

KEY MESSAGE: In this manuscript, we explored the key molecular networks for oil biosynthesis with the transcriptome and metabolome of B. napus embryo at different developmental stages. Brassica napus (B. napus) is an important oil crop worldwide, yet the molecular pathways involved in oil biosynthesis in seeds are not fully understood. In this study, we performed a combined investigation of the gene expression profiles and metabolite content in B. napus seeds at 21, 28 and 35 days after flowering (DAF), when seed oil biosynthesis takes place. The total triacylglycerol (TAG) content in seed embryos increased over the course of seed maturation, and was accompanied by changes in the fatty acid profile, an increase in lipid droplets, and a reduction in starch grains. Metabolome analysis showed that the total amino acid, free fatty acid and organic acid contents in seed embryos decreased during seed maturation. In total, the abundance of 76 metabolites was significantly different between 21 and 28 DAF, and 68 metabolites changed in abundance between 28 and 35 DAF. Transcriptome analysis showed that the set of genes differentially expressed between stages was significantly enriched in those related to lipid metabolism, transport, protein and RNA metabolism, development and signaling, covering most steps of plant lipid biosynthesis and metabolism. Importantly, the metabolite and gene expression profiles were closely correlated during seed development, especially those associated with TAG and fatty acid biosynthesis. Further, the expression of major carbohydrate metabolism-regulating genes was closely correlated with carbohydrate content during seed maturation. Our results provide novel insights into the regulation of oil biosynthesis in B. napus seeds and highlights the coordination of gene expression and metabolism in this process.

Hyperinsulinemia and thyroid peroxidase antibody in Chinese patients with papillary thyroid cancer.

This study aimed to investigate if hyperinsulinemia and/or insulin resistance was correlated with the occurrence of papillary thyroid cancer (PTC) in a group of Chinese patients. 258 inpatients were included in the study. According to the postoperative pathology results, all subjects were divided into PTC (n = 153) and control groups (with benign thyroid nodules, n = 105). Body mass index (BMI), fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid-stimulating hormone (TSH), FT4, FT3, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), serum uric acid (UA), and lipid levels. Fasting insulin levels, HOMA-IR values, TPOAb levels, serum TSH levels, and serum uric acid levels in the PTC group were higher than those in the control group (p < 0.05). However, no significant differences in age, gender, BMI, history of hypertension, and the levels of fasting plasma glucose, FT3, FT4, TGAb, total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were observed between the two groups (p > 0.05). After the multiple logistic regression analysis, the occurrence of PTC was positively associated with fasting insulin (odds ratio [OR] = 1.048, 95% confidence interval [CI]: 1.003-1.096, p = 0.037) and TPOAb levels (OR = 1.001, 95% CI: 1.000-1.002, p = 0.032). Moreover, TPOAb level was positively correlated with vague margin (r = 0.126, p = 0.045) and negatively correlated with homogeneous echo (r = -0.179, p = 0.004). However, fasting insulin levels were not correlated with pathological characteristics of PTC. Hyperinsulinemia and higher TPOAb levels might be the risk factors of PTC, but not disease severity in Chinese patients.

Whole Genome Sequencing and Analysis of Chlorimuron-Ethyl Degrading Bacteria Klebsiella pneumoniae 2N3.

Klebsiella pneumoniae 2N3 is a strain of gram-negative bacteria that can degrade chlorimuron-ethyl and grow with chlorimuron-ethyl as the sole nitrogen source. The complete genome of Klebsiella pneumoniae 2N3 was sequenced using third generation high-throughput DNA sequencing technology. The genomic size of strain 2N3 was 5.32 Mb with a GC content of 57.33% and a total of 5156 coding genes and 112 non-coding RNAs predicted. Two hydrolases expressed by open reading frames (ORFs) 0934 and 0492 were predicted and experimentally confirmed by gene knockout to be involved in the degradation of chlorimuron-ethyl. Strains of ΔORF 0934, ΔORF 0492, and wild type (WT) reached their highest growth rates after 8-10 hours in incubation. The degradation rates of chlorimuron-ethyl by both ΔORF 0934 and ΔORF 0492 decreased in comparison to the WT during the first 8 hours in culture by 25.60% and 24.74%, respectively, while strains ΔORF 0934, ΔORF 0492, and the WT reached the highest degradation rates of chlorimuron-ethyl in 36 hours of 74.56%, 90.53%, and 95.06%, respectively. This study provides scientific evidence to support the application of Klebsiella pneumoniae 2N3 in bioremediation to control environmental pollution.

Integrated metabolite profiling and transcriptome analysis reveals a dynamic metabolic exchange between pollen tubes and the style during fertilization of Brassica napus.

KEY MESSAGE: In this study, we analyzed the transcriptome and metabolite profile of the style to explore the essential metabolites and specific genes for pollen tube growth of B. napus in vivo. For sexual reproduction of flowering plants, pollen must germinate on the stigma and the pollen tube must grow through the style to deliver the sperm nuclei to the female gametophyte cells. During this process, the rapidly growing pollen tube can cover substantial distances. Despite the clear requirements for energy and cellular building blocks in this process, few studies have examined the role of metabolism in the style for pollen tube elongation. In this study, we comprehensively analyzed the transcriptome and metabolite profiles during pollen germination and pollen tube growth in the style in Brassica napus. We profiled the transcripts and metabolites stored in pollen and identified many transcripts related to metabolic pathways. Mature pollen contained low levels of nutrients, whereas the styles contained high levels of diverse nutrients. The levels of most nutrients in the style, especially metabolites for cell wall synthesis and energy metabolism, rapidly decreased at 2 h after pollination, along with pollen germination and pollen tube elongation through the style. A subset of genes involved in cell wall synthesis and nutrient transport were expressed specifically in styles at 1 h after pollination. These results demonstrated that successful fertilization involves the transcripts and nutrients stored in mature pollen, and specific gene expression and stored nutrients in the style. Therefore, these findings enhance our understanding of fertilization in B. napus.

Clinical study of the effect of refractive status on stereopsis in children with intermittent exotropia.

BACKGROUND: Many studies have shown that patients with intermittent exotropia have different degrees of damage to their stereopsis function. The purpose of this study is to explore the effect of different refractive status on stereopsis in children with intermittent exotropia(IXT). METHODS: We assessed 90 children of ages 4~ 16 years with intermittent exotropia at the Second Affiliated Hospital of Dalian Medical University during the years 2016-2017. According to their refractive status, the patients were divided into hyperopia group(spherical equivalent > or = - 1.00 diopters), myopia group(spherical equivalent < or = - 1.00 diopters), emmetropia group (spherical equivalent diopter: within ±1.00DS) and anisometropia group(binocular equivalent spherical difference > or = 1.50 diopter). The distant stereopsis of the patient was checked by the synoptophore, and the near stereopsis of the patients was checked by the Titmus stereogram. Then, we compared the difference between distant stereopsis and near stereopsis in the four groups. RESULTS: (1)The retention rates of distant stereopsis in the hyperopia group, emmetropia group, myopia group and anisometropia group were 33.3, 45.2, 34.6, and 33.3%, respectively. There was no significant difference between the groups with different refractive status. (2)The retention rates of near stereopsis in the hyperopia group, emmetropia group, myopia group and anisometropia group were 66.7, 83.9, 80.8, and 55.6%, respectively. There were statistically significant differences between the emmetropia group and the anisometropia group (P = 0.030). (3)The retention rate of distant stereopsis in children with intermittent exotropia was 37.8%, and the retention rate of near stereopsis was 74.4%. The difference between the two groups was statistically significant (P = 0.019). CONCLUSIONS: The damage to distant stereopsis in children with intermittent exotropia is more serious than that to near stereopsis. The damage to near stereopsis in children with intermittent exotropia and anisometropiais more serious.

Comparative study on the technique and efficacy of microscope-assisted MI-TLIF and naked-eye MI-TLIF in lumbar revision surgery.

BACKGROUND: Lumbar revision surgery can be performed by simple lumbar nerve decompression or lumbar interbody fusion, including percutaneous endoscopic lumbar discectomy, transforaminal lumbar interbody fusion (TLIF), etc. However, lumbar revision surgery is very difficult in surgical operation. We sought to explore the technique safety and efficacy of microscope-assisted minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) in lumbar revision surgery. METHODS: Cases of postoperative recurrence following lumbar spine surgery (n = 63) treated from December 2016 to July 2021 were retrospectively analyzed, including 24 cases of microscope-assisted MI-TLIF (microscopic group) and 39 cases of naked-eye MI-TLIF (naked-eye group). The operation time, intraoperative blood loss, incision length, postoperative drainage, length of hospital stay, initial operation, and visual analog score (VAS) of low back and leg pain before and at 7 days and 3 months after the operation and the last follow-up were compared between the two groups. The Oswestry Dysfunction Index (ODI) and the Japanese Orthopaedic Association (JOA) scores before and after the operation and the Bridwell interbody fusion grades at 1 year were compared. The independent t tests, Mann-Whitney U tests, and Chi-square tests were used for analysis. RESULTS: All 63 patients were successfully treated by operation and were followed up for an average of 31.5 ± 8.6 months (range 12-48 months). The two groups had no significant difference in sex, age, incision length, initial operation, or operative segment (P > 0.05). There was no significance in operation time, VAS score, ODI score, and JOA score of low back pain or Bridwell interbody fusion grade between the two groups (P > 0.05). Significant differences in intraoperative blood loss, postoperative drainage, and the lengths of hospital stay were observed between the two groups (P < 0.05). Cerebrospinal fluid leakage (n = 2), edema of nerve roots (n = 2), and incision infection (n = 1) were observed in the naked-eye group. There were no complications in the microscopic group, such as cerebrospinal fluid leakage, edema of nerve roots, and incision infection. CONCLUSION: Although microscope-assisted MI-TLIF and naked-eye MI-TLIF are both effective during lumbar revision surgery, microscope-assisted MI-TLIF brings less trauma, less bleeding, shorter postoperative hospital stay, and faster recovery. Unlike traditional surgery, microscope-assisted MI-TLIF provides a clear visual field, adequate hemostasis, and nerve decompression.

Biomass-related PM2.5 induced inflammatory microenvironment via IL-17F/IL-17RC axis.

Biomass exposure is a significant environmental risk factor for COPD, but the underlying mechanisms have not yet been fully elucidated. Inflammatory microenvironment has been shown to drive the development of many chronic diseases. Pollution exposure can cause increased levels of inflammatory factors in the lungs, leading to an inflammatory microenvironment which is prevalent in COPD. Our findings revealed that IL-17F was elevated in COPD, while exposure to biomass led to increased expression of IL-17F in both alveolar epithelial and macrophage cells in mice. Blocking IL-17F could alleviate the lung inflammation induced by seven days of biomass exposure in mice. We employed a transwell co-culture system to simulate the microenvironment and investigate the interactions between MLE-12 and MH-S cells. We demonstrated that anti-IL-17F antibody attenuated the inflammatory responses induced by BRPM2.5 in MLE-12 and MH-S co-cultured with BRPM2.5-MLE-12, which reduced inflammatory changes in microenvironment. We found that IL-17RC, an important receptor for IL-17F, played a key role in the interactions. Knockout of IL-17RC in MH-S resulted in inhibited IL-17F signaling and attenuated inflammatory response after MH-S co-culture with BRPM2.5-MLE-12. Our investigation suggests that BRPM2.5 induces lung epithelial-macrophage interactions via IL-17F/IL-17RC axis regulating the inflammatory response. These results may provide a novel strategy for effective prevention and treatment of biomass-related COPD.

Toward Unified AI Drug Discovery with Multimodal Knowledge.

Background: In real-world drug discovery, human experts typically grasp molecular knowledge of drugs and proteins from multimodal sources including molecular structures, structured knowledge from knowledge bases, and unstructured knowledge from biomedical literature. Existing multimodal approaches in AI drug discovery integrate either structured or unstructured knowledge independently, which compromises the holistic understanding of biomolecules. Besides, they fail to address the missing modality problem, where multimodal information is missing for novel drugs and proteins. Methods: In this work, we present KEDD, a unified, end-to-end deep learning framework that jointly incorporates both structured and unstructured knowledge for vast AI drug discovery tasks. The framework first incorporates independent representation learning models to extract the underlying characteristics from each modality. Then, it applies a feature fusion technique to calculate the prediction results. To mitigate the missing modality problem, we leverage sparse attention and a modality masking technique to reconstruct the missing features based on top relevant molecules. Results: Benefiting from structured and unstructured knowledge, our framework achieves a deeper understanding of biomolecules. KEDD outperforms state-of-the-art models by an average of 5.2% on drug-target interaction prediction, 2.6% on drug property prediction, 1.2% on drug-drug interaction prediction, and 4.1% on protein-protein interaction prediction. Through qualitative analysis, we reveal KEDD's promising potential in assisting real-world applications. Conclusions: By incorporating biomolecular expertise from multimodal knowledge, KEDD bears promise in accelerating drug discovery.

Electrochemical response mechanism of DNA damaged cells: DNA damage repair and purine metabolism activation.

In modern society, due to the sharp increase in pollutants that cause DNA damage, there is a growing demand for innovative detection techniques and biomarkers. In this paper, the electrochemical behavior of HepG2 cells exposed to CdCl2 was investigated, and the electrochemical response mechanism of DNA damage was identified by exploring the correlation between the DNA damage response and purine metabolism. Western blot analysis revealed that the expression levels of ATM and Ku70 increased at 0.3 µM CdCl2, indicating a DNA damage response and activation of DNA repair processes. Simultaneously, elevated expression levels of PRPP aminotransferase, HPRT, and XOD were observed, leading to an increase in intracellular purine levels and electrochemical signals. The expression of Ku70 peaked at 0.5 µM CdCl2, indicating the highest DNA repair activity. The expression profiles of these purine metabolism proteins mirrored those of Ku70, suggesting a strong correlation between the activation of purine metabolism and DNA damage repair. Consistently, intracellular purine levels exhibited a similar trend, leading to corresponding changes in electrochemical signals. In summary, electrochemical using intracellular purines as biomarkers has the potential to emerge as a novel method for detecting early DNA damage.

Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9.

The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis.

Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation.

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.