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Abstract Objective To explore the effects of Icaritin (ICA) on the regulation of osteocyte exosomal miRNAs and to promote the understanding of the potential molecular mechanisms involved in bone repair by ICA. Methods MLO-Y4 cells were treat with PBS or 10 µM ICA for 24 h and the supernatant was collected. Exosomes were isolated and purified according to standard methods, and identified by transmission electron microscopy, nanoparticle tracking analysis and protein blotting. Exosomal miRNAs were analysed by RNA sequencing. Results Osteocyte exosomes were successfully isolated and characterised. MiRNA sequencing showed that two known exosomal miRNAs (miR-128-3p, miR-30a-5p) were significantly up-regulated and two were significantly down-regulated (miR-5112, miR-1285) after ICA intervention. Conclusion Based on the findings, ICA regulates several miRNAs of osteocytes, which deepen our understanding of the therapeutic effects and mechanisms of ICA on skeletal diseases. The translational potential of this article Osteocytes are the most abundant cell type in bone tissue, of which the impact on bone homeostasis is still not clear. This study explored the impact of icaritin on osteocytes and their derived exosomes. By doing so, we hope to contribute to the understanding the therapeutic potential of ICA and osteocytes in maintaining bone health and treating conditions such as osteoporosis.

Abstract Background Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7). Methods To explore how cancer cells resist immune cell-mediated ferroptosis, we used a comprehensive range of techniques. We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rora fl mice. Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry. Results PD1-resistant tumors upregulate Fabp7, driving protective metabolic changes that shield cells from ferroptosis and evade anti-tumor immunity. Fabp7 decreases the transcription of ferroptosis-inducing genes like Lpcat3 and increases the transcription of ferroptosis-protective genes such as Bmal1 through epigenetic reprogramming. Lipidomic profiling revealed that Fabp7 increases triglycerides and monounsaturated fatty acids (MUFAs), which impede lipid peroxidation and ROS generation. Fabp7 also improves mitochondrial function and fatty acid oxidation (FAO), enhancing cancer cell survival. Furthermore, cancer cells increase Fabp7 expression in CD8+ T cells, disrupting circadian clock gene expression and triggering apoptosis through p53 stabilization. Clinical trial data revealed that higher FABP7 expression correlates with poorer overall survival and progression-free survival in patients undergoing immunotherapy. Conclusions Our study uncovers a novel mechanism by which cancer cells evade immune-mediated ferroptosis through Fabp7 upregulation. This protein reprograms lipid metabolism and disrupts circadian regulation in immune cells, promoting tumor survival and resistance to immunotherapy. Targeting Fabp7 could enhance immunotherapy effectiveness by re-sensitizing resistant tumors to ferroptosis.

Abstract Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stress model. Among 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient male mouse liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency in hepatocytes abolishes Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) secretion while maintaining partial ApoB-48 VLDL secretion. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway.

Abstract The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions. These three hZAC structures display highly similar conformations to one another, forming symmetrical homo-pentamers with a central ion-conduction pore. The hZAC protomer comprises an extracellular domain (ECD) and a transmembrane domain (TMD), sharing more structural similarity with anion-permeable CLRs, such as glycine receptors and type A γ-aminobutyric acid receptors. Notably, hZAC possesses a distinctive C-tail that establishes a disulfide bond with the loop M2-M3 in the TMD and occupies what is typically the canonical neurotransmitter orthosteric site in other mammalian CLRs. Moreover, the tip of the cys-loop creates an unprecedented orthosteric site in hZAC. The binding of Zn2+ triggers a conformational shift in the cys-loop, which presumably prompts the loop M2-M3 to move and open the channel gate. This study sheds light on the assembly of the channel, its structural features, and the process of signal transduction in hZAC.

ObjectiveTo compare the dosimetric characteristics of thyroid between intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in patients with left-sided breast cancer after modified radical mastectomy.MethodsThirty patients with left-sided breast cancer who underwent adjuvant radiotherapy after modified radical mastectomy at the Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, from December 2021 to May 2023, were selected as the study subjects, and IMRT and VMAT were used with a target prescription dose of 50 Gy/25 times. The target dose parameters of the two plans, including the mean dose (Dmean) and the dose-volume limit for organs at risk (Vx, x represents dose), were compared. ResultsThe conformity index of VMAT was higher than that of IMRT (P＜0.001). Compared with VMAT, IMRT plan significantly reduced the V5、V10、Dmean of heart, the V5 of right lung and the Dmean of right breast, while it significantly increased the V20 of left lung (P＜0.001). There was no statistically significant difference in V5 and V10 of the left thyroid between IMRT and VMAT. However, the V20, V30, V40, and Dmean of left and whole thyroid, and the V10 and Dmean of right thyroid were significantly lower in IMRT than those in VMAT (P＜0.001). ConclusionsBoth IMRT and VMAT plans can meet the clinical dosimetric requirements, among which IMRT has lower thyroid exposure dose and is more suitable for patients with high cardiac requirements.

Abstract Concessions—defined as the urban elements built by Western powers while ‘occupying’ various parts of the Chinese territory—have recently been granted heritage status by the Chinese national and local authorities. However, in many respects, they are ‘dissonant’ heritage sites since they are the result of the several-decade-long ‘colonial’ presence in Tianjin of nine foreign powers. The aim of this study is to understand how former international concessions are featured in museums and interpretation centres in present-day Tianjin. Using an approach that draws on dissonant heritage; literature on postcolonial museums, nostalgia and forgetting mechanisms; and the relationship between museographic narratives and patriotism, this article analyses a corpus of eight museums located in three former international concessions (Marshal Zhang’s Mansion, the Former Residence of Ma Zhanshan, the Museum of Modern History of Tianjin, the Five Avenues History Museum, the Museum of the Department Store Quan Ye Chang, Zhang House, the Astor Hotel Museum, the Tianjin Planning Exhibition Hall and the Tianjin Museum). The analysis is based on a common observation grid and semidirect interviews conducted with museum staff. The article captures and examines the main narratives from three perspectives: 1) revisiting the concession period as evidence of the beginning of modernity in China, which was a time in which celebrity life stories and the emergence of modern urban elements were praised; 2) considering the concessions as a dreamlike past of ‘others’ and ‘elsewheres’ belonging to a ‘foreign land’ and a context far removed from contemporary life in China, which favours the thematisation and leisure of Western architecture; and 3) selecting and targeting narratives focused on the heroes of the Republic of China (1912–1949) and the People’s Republic of China. This paper highlights and further develops how former Western concessions are imbued with a sense of both nostalgia and patriotism and sets out to gain a deeper understanding of the tension between these two attitudes.

Abstract The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17α-MHCKO) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17fl/fl and A17α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

There remains a substantial knowledge gap in understanding the coexistence effects of Microplastics (MPs), lead (Pb) and arsenic (As), which are ubiquitous environmental contaminants. Here, zebrafish (Danio rerio) embryos were used to investigate the impact of triple combined exposure to MPs (50 μg/L), Pb2+ (10 μg/L) and As3+ (200 μg/L) on the developmental responses. Survival and hatching rates were notably reduced to 32.7 % and 58.8 %, respectively. Meanwhile, the frequency of spontaneous tail contractions increased by 8.1 %, whereas heart rate and body length decreased by 4.4 % and 5.1 %, respectively. These findings demonstrated that the triple exposure markedly disrupted developmental processes and altered behavioral profiles in zebrafish larvae. Furthermore, 16 S rRNA sequencing revealed that the metabolic processes of glutathione and xenobiotics, as well as intracellular iron transport, were significantly impacted, triggering ferroptosis in the larvae exposed to triple combination. Collectively, the co-exposure to MPs, Pb2+ and As3+ even at low concentrations could significantly disrupt the developmental progress and biological functioning during the early stages of zebrafish. This will help guide future comprehensive studies on the impact of triple combined exposure during early developmental stages.

Geo-registration is a fundamental process seamlessly integrating digital information within the physical world in Mobile Augmented Reality (MAR). Achieving high precision, real-time capability, and strong adaptability in geo-registration is crucial for the effective functioning of MAR applications, especially in outdoor environments. However, existing methods frequently struggle with inaccuracies in long-distance positioning and latency of pose estimation, compounded by their sensitivity to scale changes of outdoor environment. This study addresses these challenges by proposing a novel continuous and real-time MAR geo-registration method for outdoor applications. Our approach integrates real-time kinematic Global Navigation Satellite System (RTK-GNSS) fusion with geodesic equations and rotation invariance estimation. This method substantially surpasses traditional methods, achieving 0.05 m virtual-real position accuracy (approximately six times better) and under 0.2° pose accuracy (nearly a fivefold improvement). Additionally, it exhibits superior robustness in complex MAR scenarios. Beyond improved accuracy, this method reduces the reliance on high-quality sensor hardware and precise calibration, making it suitable for various AR systems, including smartphones and tablets.

Dietary nutrient manipulation (e.g. protein fractions) could lower the environmental footprints of ruminants, especially reactive nitrogen (N). This study investigated the impacts of dietary soluble protein (SP) levels with decreased crude protein (CP) on intestinal N absorption, hindgut N metabolism, fecal microbiota and metabolites, and their linkage with N metabolism phenotype. Thirty-two male Hu sheep, with an age of six months and an initial BW of 40.37 ± 1.18 kg, were randomly assigned to four dietary groups. The control diet (CON), aligning with NRC standards, maintained a CP content of 16.7% on a dry matter basis. Conversely, the experimental diets (LPA, LPB, and LPC) featured a 10% reduction in CP compared with CON, accompanied by SP adjustments to 21.2%, 25.9%, and 29.4% of CP, respectively. Our results showed that low-protein diets led to significant reductions in the concentrations of plasma creatinine, ammonia, urea N, and fecal total short-chain fatty acids (SCFA) (P

Abstract Insecticide resistance has been a problem in both the agricultural pests and vectors. Revealing the detoxification mechanisms may help to better manage insect pests. Here, we showed that arylalkylamine N-acetyltransferase 1 (AANAT1) regulates intestinal detoxification process through modulation of reactive oxygen species (ROS)-activated transcription factors cap“n”collar isoform-C (CncC): muscle aponeurosis fibromatosis (Maf) pathway in both the oriental fruit fly, Bactrocera dorsalis, and the arbovirus vector, Aedes aegypti. Knockout/knockdown of AANAT1 led to accumulation of biogenic amines, which induced a decreased in the gut ROS level. The reduced midgut ROS levels resulted in decreased expression of CncC and Maf, leading to lower expression level of detoxification genes. AANAT1 knockout/knockdown insects were more susceptible to insecticide treatments. Our study reveals that normal functionality of AANAT1 is important for the regulation of gut detoxification pathways, providing insights into the mechanism underlying the gut defense against xenobiotics in metazoans.

Abstract Two‐dimensional (2D) semiconductors, such as monolayer MoS2, has emerged as a profound material platform in the post‐Moore era due to their versatile applications for high‐performance transistors, memories, photodetectors, neuristors, and so on. Nevertheless, the inherent defects in these atomically thin materials have given rise to significant hysteresis in their field‐effect transistors (FETs), resulting in shifted threshold voltages and elevated power consumptions not only on single‐device levels but also at circuitry scales. We herein report that, by vertically integrating an in‐plane ferroelectric, NbOCl2, with monolayer MoS2 FETs, the hysteresis in both the output and transfer curves of the latter can be greatly suppressed, which we attribute to compensated electromigration currents by the polarization currents of the 2D ferroelectric. This work opens a new avenue to hysteresis‐free 2D transistors without necessitating defect‐free channels, thus allowing for their use in high driving‐voltage scenarios such as power electronics.

Long-term exposure of the peritoneum to peritoneal dialysate results in pathophysiological changes in the anatomical organization of the peritoneum and progressive development of peritoneal fibrosis. This leads to a decline in peritoneal function and ultrafiltration failure, ultimately necessitating the discontinuation of peritoneal dialysis, severely limiting the potential for long-term maintenance. Additionally, encapsulating peritoneal sclerosis, a serious consequence of peritoneal fibrosis, resulting in patients discontinuing PD and significant mortality. The causes and mechanisms underlying peritoneal fibrosis in patients undergoing peritoneal dialysis remain unknown, with no definitive treatment available. However, abnormal activation of the immune system appears to be involved in altering the structure of the peritoneum and promoting fibrotic changes. Macrophage infiltration and polarization are key contributors to pathological injury within the peritoneum, showing a strong correlation with the epithelial-to-mesenchymal transition of mesothelial cells and driving the process of fibrosis. This article discusses the role and mechanisms underlying macrophage activation-induced peritoneal fibrosis resulting from PD by analyzing relevant literature from the past decade and provides an overview of recent therapeutic approaches targeting macrophages to treat this condition.

The goal of combination cancer therapy, including chemo-phototherapy, is to achieve highly efficient antitumor effects while minimizing the adverse reactions associated with conventional chemotherapy. Nevertheless, enhancing the contribution of non-chemotherapeutic strategies in combination therapy is often challenging because this requires multiple active ingredients to be encapsulated in a single delivery system. However, most commonly used photothermal reagents are challenging to be loaded in large quantities and have poor biocompatibility. Herein, we developed photothermal co-micelles through a co-assembly strategy using a cholesterol-based liquid crystal block copolymer (LC-BCP) with disulfide bonds in the side chain of the LC blocks and a croconaine-based amphiphile (CBA) containing a cholesterol moiety. This approach allowed the CBA to be effectively embedded within LC-BCPs, serving as the functional component of the drug-loaded carrier. These co-micelles could encapsulate doxorubicin (DOX), showed tunable reduction-responsive drug release, and enabled near-infrared laser-triggered photothermal therapy as well as in vivo fluorescence and photothermal imaging. Following laser irradiation, the photothermal activity of the co-micelles rapidly induced tumor cell death and accelerated drug release. In vitro and in vivo experiments demonstrated that the synergistic photo-chemotherapeutic effects of these drug-loaded co-micelles offer a promising avenue for synergistic precision photothermal-chemotherapy.

Summary: Tank-binding kinase 1 (TBK1) is a critical signal transducer in the nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, essential for innate immunity. However, its negative regulation mechanisms remain unclear. This study demonstrates that TBK1 succinylation, regulated by desuccinylase SIRT5, inhibits lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated NF-κB and IRF signaling activation. We identified three key succinylation sites on TBK1: K38, K154, and K692. In endotoxemia and sepsis models, reduced SIRT5 levels in macrophages increased TBK1 succinylation, inhibiting its binding to IRF3 and TRAF2 and suppressing the inflammatory response. In vivo, adoptive transfer of macrophages expressing the succinylation-resistant TBK1-2KR (K154/692R) mutant reversed the inflammatory cytokine suppression caused by SIRT5 deficiency, exacerbating sepsis-induced lung injury. These findings reveal a novel mechanism by which SIRT5 modulates TBK1 activity and macrophage-mediated inflammation during sepsis.

Abstract Protein surfaces have pivotal roles in interactions between proteins and other biological molecules. However, the structural dynamics of protein surfaces have rarely been explored and are poorly understood. Here, the surface of a single‐stranded DNA (ssDNA) binding protein (SSB) with four DNA binding domains that bind ssDNA in binding site sizes of 35, 56, and 65 nucleotides per tetramer is investigated. Using oligonucleotides as probes to sense the charged surface, NaCl induces a two‐state structural transition on the SSB surface even at moderate concentrations. Chelation of sodium ions with charged amino acids alters the network of hydrogen bonds and/or salt bridges on the surface. Such changes are associated with changes in the electrostatic potential landscape and interaction mode. These findings advance the understanding of the molecular mechanism underlying the enigmatic salt‐induced transitions between different DNA binding site sizes of SSBs. This work demonstrates that monovalent salt is a key regulator of biomolecular interactions that not only play roles in non‐specific electrostatic screening effects as usually assumed but also may configure the surface of proteins to contribute to the effective regulation of biomolecular recognition and other downstream events.

BackgroundThere is a high morbidity of polyps in the digestive tract, and certain subtypes of polyps are thought to induce cancer progression and often recur, which may be associated with chronic inflammation. Mendelian randomization (MR) can help identify potential causative relationships and inform early treatment action.MethodsWe performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and three types of polyps from European ancestry, respectively, including gastric polyp (6,155 cases vs. 341,871 controls), colonic polyp (22,049 cases vs. 332,368 controls) and gallbladder polyp (458 cases vs. 340,083 controls). Inverse-variance weighted (IVW), weight median (WM), and MR-Egger methods were used for calculating causal estimates. Furthermore, Bayesian model averaging MR (MR-BMA) method was employed to detect the dominant causal circulatory cytokines with adjustment for pleiotropy effects.ResultsOur univariable MR using inverse-variance weight method identified causal associations of IL-2ra (OR: 0.892, 95%CI: 0.828–0.961, p = 0.003), MIG (OR: 1.124, 95%CI: 1.046–1.207, p = 0.001) and IL-18 (OR: 0.912, 95%CI: 0.852–0.977, p = 0.008) with gastric polyp, MIP1b (OR: 0.956, 95%CI: 0.927–0.987, p = 0.005) and IL-6 (OR: 0.931, 95%CI: 0.870–0.995, p = 0.035) with colonic polyp and IL-9 (OR: 0.523, 95%CI: 0.345–0.794, p = 0.0007) with gallbladder polyp. Finally, our MR-BMA analysis prioritized MIG (MIP = 0.332, MACE = 0.022; PP: 0.264, MSCE = 0.059), IL-18 (MIP = 0.302, MACE = −0.020; PP: 0.243, MSCE = −0.059) and IL-2ra (MIP: 0.129; MACE: −0.005; PP: 0.112, MSCE: −0.031) for gastric polyp, and MIP1b (MIP = 0.752, MACE = −0.033; PP: 0.665, MSCE = −0.044) and IL-6 (MIP: 0.196; MACE: −0.012; PP: 0.140, MSCE: −0.064) for colonic polyp, and IL-9 (MIP = 0.936, MACE = −0.446; PP: 0.781, MSCE = −0.478) for gallbladder polyp as the top-ranked protective factors.ConclusionOur research advances the current understanding of the function of certain inflammatory biomarker pathways in the genesis and malignant mutation of polyps in the digestive tract. Deeper substantiation is necessary to assess the potential of these cytokines as pharmacological or lifestyle targets for digestive polyps prevention.

It has been proven that robot-assisted rehabilitation training can effectively promote the recovery of upper-limb motor function in post-stroke patients. Increasing patients’ active participation by providing assist-as-needed (AAN) control strategies is key to the effectiveness of robot-assisted rehabilitation training. In this paper, a greedy assist-as-needed (GAAN) controller based on radial basis function (RBF) network combined with 3 degrees of freedom (3-DOF) potential constraints was proposed to provide AAN interactive forces of an end-effect upper limb rehabilitation robot. The proposed 3-DOF potential fields were adopted to constrain the tangential motions of three kinds of typical target trajectories (one-dimensional (1D) lines, two-dimensional (2D) curves and three-dimensional (3D) spirals) while the GAAN controller was designed to estimate the motor capability of a subject and provide appropriate robot-assisted forces. The co-simulation (Adams-Matlab/Simulink) experiments and behavioral experiments on 10 healthy volunteers were conducted to validate the utility of the GAAN controller. The experimental results demonstrated that the GAAN controller combined with 3-DOF potential field constraints enabled the subjects to actively participate in kinds of tracking tasks while keeping acceptable tracking accuracies. 3D spirals could be better in stimulating subjects’ active participation when compared to 1D and 2D target trajectories. The current GAAN controller has the potential to be applied to existing commercial upper limb rehabilitation robots.

ABSTRACT Background Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co‐morbidities are lacking. Methods We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross‐trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross‐phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome‐wide association study (TWAS) to determine whether their cross‐organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD. Results We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD. Conclusions We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.

In a study of DNA methylation changes in melatonin-deficient rice mutants, mutant plants showed premature leaf senescence during grain-filling and reduced grain yield. Melatonin deficiency led to transcriptional reprogramming, especially of genes involved in chlorophyll and carbon metabolism, redox regulation, and transcriptional regulation, during dark-induced leaf senescence. Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes. Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin. A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Background and objective Bone is a common site for metastasis in lung adenocarcinoma, but the mechanism behind lung adenocarcinoma bone metastasis is still unclear. And currently, there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models, which limits the research on the mechanism of lung adenocarcinoma bone metastasis. The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone, labeled with green fluorescent proteins (GFP) and fireflies luciferase (LUC), along with transcriptomic characterization, would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods. Methods The human lung adenocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model, and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3; cell counting kit-8 (CCK-8), colony formation assay, scratch wound assays, Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells. A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing. Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established. Compared to parental cells, this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation, migration, and invasion abilities. Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells, with 1021 genes up-regulated and 1933 genes down-regulated. Gene Ontology (GO) functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery. The molecular functions identified as significantly enriched included signaling receptor activity, calcium ion binding, and extracellular matrix structural constituent. Additionally, the biological processes found to be enriched were cell adhesion and biological adhesion. The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiotics by cytochrome P450, retinol metabolism, drug metabolism-cytochrome P450, cell adhesion molecules, steroid hormone biosynthesis, and the nuclear factor kappa B (NF-κB) signaling pathway. Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established. The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

Abstract Background Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure. Results Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being first enhanced in the microspore and subsequently decreased in sperm. Functional analysis of rice CHG methyltransferase genes CMT3a and CMT3b indicates that CMT3a functions as the major CHG methyltransferase in rice meiocyte, while CMT3b is responsible for the increase of CHG methylation in microspore. The function of the two histone demethylases JMJ706 and JMJ707 that remove H3K9me2 may contribute to the decreased CHG methylation in sperm. During male gametogenesis CMT3a mainly silences TE and TE-related genes while CMT3b is required for repression of genes encoding factors involved in transcriptional and translational activities. In addition, CMT3b functions to repress zygotic gene expression in egg and participates in establishing the zygotic epigenome upon fertilization. Conclusion Collectively, the results indicate that DNA methylation is dynamically remodeled during male gametogenesis, distinguish the function of CMT3a and CMT3b in sex cells, and underpin the functional significance of DNA methylation remodeling during rice reproduction.

Cupriavidus necator can produce single-cell proteins (SCPs) using electrons produced by hydrogen as energy, oxygen as electron acceptors, and CO2 as carbon sources. Gas fermentation is a process of microbial fermentation that uses gas substrates (such as hydrogen, carbon dioxide, etc.) which faces several challenges, mainly including the low solubility of gas substrates, the danger of hydrogen and oxygen mixing, and the optimization of fermentation conditions. To overcome these challenges, this article explores a variety of strategies—including the design of a self-developed bioreactor—to reduce the risk of static electricity. Without the addition of filler material, the results showed that the maximum cell dry weight (CDW) of 30% secondary seed inoculation was 20.41% higher than that of 10% secondary seed inoculum, and 5.99% higher than that of 20% secondary seed inoculum. Combined with the filler material and with the use of high-efficiency continuous fermentation technology, the average yield of continuous fermentation was 23.31 g/day, while the average yield of batch fermentation was 14.33 g/day. The daily yield of continuous fermentation is 1.63 times that of batch fermentation. These efforts are aimed at improving the efficiency and safety of gas fermentation.