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Abstract Digital image steganography serves as a technology facilitating covert communication through digital images by subtly incorporating secret data into a cover image. This practice poses a potential threat, as criminals exploit steganography to transmit illicit content, thereby jeopardizing information security. Consequently, it becomes imperative to implement defensive strategies against steganographic techniques. This paper proposes a novel defense mechanism termed “image vaccine” to safeguard digital images from steganography. The process of “vaccinating” an image renders it immune to steganographic manipulation. Notably, when criminals attempt to embed secret data into vaccinated images, the presence of such hidden information can be detected with a 100% probability, ensuring the consistent identification of stego images. This proactive approach enables the interception of stego image transmission, thereby neutralizing covert communication channels.

Abstract Background The updated status of hypertension and its risk factors are poorly evaluated in Tibetan highland areas. We initiated a large-scale cross-sectional survey to provide updated status of hypertension and its risk factors (especially salt intake) in the Ganzi Tibetan Plateau, China. Methods Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents from 4 counties in the Ganzi Tibetan area. The whole survey population was used to present the epidemiology and risk factors of hypertension. The participants with blood and urine biochemistry data were used to analyze the relationship between salt intake parameters and hypertension. Results Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents. The overall prevalence rate of hypertension was 33.5% (the age-adjusted prevalence rate was 28.9%). A total of 50.9% of the hypertensive patients knew their conditions; 30.1% of them received antihypertensive treatment; and 11.2% of them had their blood pressure controlled. Age, male sex, living altitude ≥ 3500 m, overweight and abdominal obesity were positively correlated with hypertension. In addition, the adjusted odds ratio (OR) for hypertension was 1.33 (95% CI: 1.01–1.74) for drinking tea with salt, and 1.51 (95% CI: 1.32–1.72) for per SD increase in the estimation of 24-hour urinary sodium excretion (e24hUSE). Furthermore, per 100mmol/day increase in e24hUSE was associated with elevation of blood pressure (+ 10.16, 95% CI: 8.45–11.87 mmHg for SBP; +3.83, 95% CI: 2.74–4.93 mmHg for DBP) in this population. Conclusions Our survey suggests a heavy disease burden of hypertension in the Ganzi Tibetan Plateau. Age, male sex, altitude of residence ≥ 3500 m, overweight, abdominal obesity, and excessive salt intake (shown as drinking tea with adding salt and a higher level of e24hUSE) all increased the risk of hypertension in this highland area.

Abstract The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called “quasiparticle poisoning”. Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.

Abstract Kidney fibrosis is considered to be the ultimate aggregation pathway of chronic kidney disease (CKD), but its underlying mechanism remains elusive. Protein kinase C-delta (PKC-δ) plays critical roles in the control of growth, differentiation, and apoptosis. In this study, we found that PKC-δ was highly upregulated in human biopsy samples and mouse kidneys with fibrosis. Rottlerin, a PKC-δ inhibitor, alleviated unilateral ureteral ligation (UUO)-induced kidney fibrosis, inflammation, VDAC1 expression, and cGAS-STING signaling pathway activation. Adeno-associated virus 9 (AAV9)-mediated VDAC1 silencing or VBIT-12, a VDAC1 inhibitor, attenuated renal injury, inflammation, and activation of cGAS-STING signaling pathway in UUO mouse model. Genetic and pharmacologic inhibition of STING relieved renal fibrosis and inflammation in UUO mice. In vitro, hypoxia resulted in PKC-δ phosphorylation, VDAC1 oligomerization, and activation of cGAS-STING signaling pathway in HK-2 cells. Inhibition of PKC-δ, VDAC1 or STING alleviated hypoxia-induced fibrotic and inflammatory responses in HK-2 cells, respectively. Mechanistically, PKC-δ activation induced mitochondrial membrane VDAC1 oligomerization via direct binding VDAC1, followed by the mitochondrial DNA (mtDNA) release into the cytoplasm, and subsequent activated cGAS-STING signaling pathway, which contributed to the inflammation leading to fibrosis. In conclusion, this study has indicated for the first time that PKC-δ is an important regulator in kidney fibrosis by promoting cGAS-STING signaling pathway which mediated by VDAC1. PKC-δ may be useful for treating renal fibrosis and subsequent CKD.

Abstract Heat shuttling phenomenon is characterized by the presence of a non-zero heat flow between two bodies without net thermal bias on average. It was initially predicted in the context of nonlinear heat conduction within atomic lattices coupled to two time-oscillating thermostats. Recent theoretical works revealed an analog of this effect for heat exchanges mediated by thermal photons between two solids having a temperature dependent emissivity. In this paper, we present the experimental proof of this effect using systems made with composite materials based on phase change materials. By periodically modulating the temperature of one of two solids we report that the system akin to heat pumping with a controllable heat flow direction. Additionally, we demonstrate the effectiveness of a simultaneous modulation of two temperatures to control both the strength and direction of heat shuttling by exploiting the phase delay between these temperatures. These results show that this effect is promising for an active thermal management of solid-state technology, to cool down solids, to insulate them from their background or to amplify heat exchanges.

Abstract Background The public health service capability of primary healthcare personnel directly affects the utilization and delivery of health services, and is influenced by various factors. This study aimed to examine the status, factors, and urban-rural differences of public health service capability among primary healthcare personnel, and provided suggestions for improvement. Methods We used cluster sampling to survey 11,925 primary healthcare personnel in 18 regions of Henan Province from 20th to March 31, 2023. Data encompassing demographics and public health service capabilities, including health lifestyle guidance, chronic disease management, health management of special populations, and vaccination services. Multivariable regression analysis was employed to investigate influencing factors. Propensity Score Matching (PSM) quantified urban-rural differences. Results The total score of public health service capability was 80.17 points. Chronic disease management capability scored the lowest, only 19.60. Gender, education level, average monthly salary, professional title, health status, employment form, work unit type, category of practicing (assistant) physician significantly influenced the public health service capability (all P

Abstract Cholesterol metabolism reprogramming is one of the significant characteristics of hepatocellular carcinoma (HCC). Cholesterol increases the risk of epithelial–mesenchymal transition (EMT) in cancer. Sterol O-acyltransferases 1 (SOAT1) maintains the cholesterol homeostasis. However, the exact mechanistic contribution of SOAT1 to EMT in HCC remains unclear. Here we demonstrated that SOAT1 positively related to poor prognosis of HCC, EMT markers and promoted cell migration and invasion in vitro, which was mediated by the increased cholesterol in plasmalemma and cholesterol esters accumulation. Furthermore, we reported that SOAT1 disrupted cholesterol metabolism homeostasis to accelerate tumorigenesis and development in HCC xenograft and NAFLD-HCC. Also, we detected that nootkatone, a sesquiterpene ketone, inhibited EMT by targeting SOAT1 in vitro and in vivo. Collectively, our finding indicated that SOAT1 promotes EMT and contributes to hepatocarcinogenesis by increasing cholesterol esterification, which is suppressed efficiently by nootkatone. This study demonstrated that SOAT1 is a potential biomarker and therapeutic target in NAFLD-HCC and SOAT1-targeting inhibitors are expected to be the potential new therapeutic treatment for HCC.

Summary: Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B–E (GSDMB–GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.

Abstract Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia–reperfusion (I/R) injury, we found that the prophylactic administration of a well‐known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R‐induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro‐inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen‐glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R‐induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Alzheimer′s disease(AD) is a widely recognized chronic neurodegenerative condition.Drosophila, with its well-defined genetic structure, straightforward experimental methodologies, and the presence of human disease-related genes or highly similar homologous genes, serves as an advantageous model organism.The utilization of Drosophila′s renowned Galactose-regulated Upstream Promoter Element 4-Upstream Activating Sequence(GAL4-UAS) system has led to the development of various AD models.These models facilitate the exploration of AD′s molecular mechanisms and the advancement of drug discovery efforts.This paper reviews the foundational principles, methodologies, and diverse applications of different AD Drosophila models, offering insights and innovative approaches for AD research utilizing Drosophila.

Abstract Lysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8–lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.

Abstract The slip systems and motion behavior of dislocations induced by nano-indentation technique in GaN-based LDs were investigated. Dislocations with burgers vector of b = 1/3 were introduced on either {11 $$\overline{2}$$ 2 ¯ 2} , or {1 $$\overline{1}$$ 1 ¯ 01} pyramidal slip systems in the upper p-GaN layer. Besides, {0001} basal slip system was also activated. The AlGaN/InGaN multi-layers in device can provide mismatch stresses to prevent dislocations from slipping through. It was observed that the density of dislocations induced by the indenter significantly decreased from the upper to the lower regions of the multi-layers. The a + c dislocations on pyramidal slip planes were mostly blocked by the strained layers.

Abstract Previous studies examining the association between hemoglobin concentration and hypertension have yielded inconsistent results. There is still a lack of evidence regarding the association between hemoglobin concentration and hypertension risk in native Tibetans at high altitude. We performed this cross‐sectional study in Luhuo County of Ganzi Tibetan Autonomous Prefecture (average altitude of 3500 m). In this study, we enrolled 1547 native Tibetans. The association between hemoglobin concentration and hypertension risk was examined by multivariate binary logistic regression and smooth curve fitting. Native Tibetans with hypertension had significantly higher hemoglobin concentrations than those without hypertension (165.9 ± 21.5 g/L vs. 157.7 ± 19.2 g/L, P

The heat shock protein 70 (HSP70) gene family plays a crucial role in the response of organisms to environmental stress. However, it has not been systematically characterized in shrimp. In this study, we identified 25 PcHsp70 genes in the Penaeus chinensis genome. The encoded proteins were categorized into six subgroups based on phylogenetic relationships. Tandem duplication was the main driver of amplification in the PcHsp70 family, and the genes have experienced strong purifying selection during evolution. Transcriptome data analysis revealed that the 25 PcHsp70 members have different expression patterns in shrimp under conditions of low temperature, low salinity, and white spot syndrome virus infection. Among them, PcHsp70.11 was significantly induced under all three stress conditions, suggesting that this gene plays an important role in response to environmental stress in P. chinensis. To the best of our knowledge, this is the first study to systematically analyze the Hsp70 gene family in shrimp. The results provide important information on shrimp Hsp70s, contributing to a better understanding of the role of these genes in environmental stress and providing a basis for further functional studies.

Abstract Electrochemical activation usually accompanies in situ atom rearrangement forming new catalytic sites with higher activity due to reconstructed atomic clusters or amorphous phases with abundant dangling bonds, vacancies, and defects. By harnessing the pre‐catalytic process of reconstruction, a multilevel structure of CuNi alloy nanoparticles encapsulated in N‐doped carbon (CuNi nanoalloy@N/C) transforms into a highly active compound of Ni‐doped CuO nanocluster supported on (N/O‐C) co‐doped C. Both the exposure of accessible active sites and the activity of individual active sites are greatly improved after the pre‐catalytic reconstruction. Manipulating the Cu/Ni ratios of CuNi nanoalloy@N/C can tailor the electronic property and d‐band center of the high‐active compound, which greatly optimizes the energetics of oxygen evolution reaction (OER) intermediates. This interplay among Cu, Ni, C, N, and O modifies the interface, triggers the active sites, and regulates the work functions, thereby realizing a synergistic boost in OER.

Cisplatin-induced acute kidney injury (CIAKI) is a major dose-limiting toxicity of cisplatin treatment. The mechanisms of CIAKI involve the production of inflammation, apoptosis and oxidative stress. Palmatine, an isoquinoline alkaloid has anti-inflammatory activity. Here, we investigated the protective effect and underlying mechanism of palmatine on CIAKI by in vitro and in vivo experiments based on network pharmacology. Network pharmacology was used to analyze the relationship and potential mechanisms of palmatine and CIAKI. The protective effect of palmatine was validated in cisplatin induced 293 T cell injury model and mice model. Furthermore, the mechanism of palmatine on CIAKI was determined by detecting inflammatory factors and related signaling pathways. A total of 61 targets of palmatine against CIAKI and the closely related signaling pathways including oxidative stress, MAPK and Akt were found. Palmatine effectively protected 293 T cells and mouse kidney against CIAKI. Mechanistically, palmatine reduced CIAKI inflammation by suppressing the NF-κB/MAPK pathway. Meanwhile, palmatine inhibited apoptosis by activating the Akt pathway and reduced oxidative stress. The results of in vitro and in vivo experiments were consistent with those of network pharmacology. Furthermore, the cytotoxicity of cisplatin to H460 and HCT116 cells was slightly improved by palmatine. In conclusion, palmatine protects against CIAKI by inhibiting inflammation and apoptosis through regulation of NF-κB/MAPK and Akt pathways. Palmatine is a potential adjunctive treatment during the use of cisplatin.

Summary: Hepatitis B virus (HBV) infection generally elicits weak type-I interferon (IFN) immune response in hepatocytes, covering the regulatory effect of IFN-stimulated genes. In this study, low level of IFN-stimulated gene 12a (ISG12a) predicted malignant transformation and poor prognosis of HBV-associated hepatocellular carcinoma (HCC), whereas high level of ISG12a indicated active NK cell phenotypes. ISG12a interacts with TRIM21 to inhibit the phosphorylation activation of protein kinase B (PKB, also known as AKT) and β-catenin, suppressing PD-L1 expression to block PD-1/PD-L1 signaling, thereby enhancing the anticancer effect of NK cells. The suppression of PD-1-deficient NK-92 cells on HBV-associated tumors was independent of ISG12a expression, whereas the anticancer effect of PD-1-expressed NK-92 cells on HBV-associated tumors was enhanced by ISG12a and treatments of atezolizumab and nivolumab. Thus, tumor intrinsic ISG12a promotes the anticancer effect of NK cells by regulating PD-1/PD-L1 signaling, presenting the significant role of innate immunity in defending against HBV-associated HCC.

Nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC) are subtypes of head and neck cancer with different treatment effects due to the heterogeneity of tumor microenvironments. This study was to investigate the distinctive tumor microenvironments of NPC and OPC. Analyzing single-cell data from 10 cases of each subtype, we reveal significant differences in cellular composition, with NPC microenvironment dominated by T/NK and B cells, and OPC characterized by prevalent epithelial cells and fibroblasts. Dynamic transitions of CD8 T cells are observed in both tumor types, involving shifts from naivety to cytotoxicity, proliferation, and eventual exhaustion/exhausted states. Additionally, Tregs exhibit heightened proliferative abilities in later developmental stages, concomitant with exhaustion. These highly proliferative T cells and Tregs manifest elevated glycolysis and lactate metabolism activities. Furthermore, we explore intercellular communication between glycolytic malignant epithelial cells and these proliferative T cells. These findings offer comprehensive insights into the heterogeneity of tumor microenvironments and provide a solid foundation for future therapeutic strategies and targeted interventions.

Cytokine-like protein 1 (CYTL1) expression is deliberately downregulated during the progression of multiple types of cancers, especially breast cancer. However, the metabolic characteristics of cancer progression remain unclear. Here, we uncovered a risk of breast cancer cells harboring low CYTL1 expression, which is metabolically controlled during malignant progression. We performed metabolism comparison and revealed that breast cancer cells with low CYTL1 expression have highly suppressed transsulfuration activity that is driven by cystathionine β-synthase (CBS) and contributes to de novo cysteine synthesis. Mechanistically, CYTL1 activated Nrf2 by promoting autophagic Keap1 degradation, and Nrf2 subsequently transactivated CBS expression. Due to the lack of cellular cysteine synthesis, breast cancer cells with low CYTL1 expression showed hypersensitivity to system xc− blockade-induced ferroptosis in vitro and in vivo. Silencing CBS counteracted CYTL1-mediated ferroptosis resistance. Our results show the importance of exogeneous cysteine in breast cancer cells with low CYTL1 expression and highlight a potential metabolic vulnerability to target.

The effect of the combination of 10-Hydroxycamptothecin (HCPT) and crizotinib (CRI) on EGFR- and KRAS-mutant lung cancer cells was investigated and the conjugates of the two drugs were synthesised. HCPT combined with CRI synergistically inhibited the cell growth and proliferation of H1975, HCC827, and H460 without aggravating adverse effect on the normal cells. The combination synergistically enhanced the cell apoptosis rate through releasing Cyto-C by activation of Bcl-2 family-mediated mitochondrial signalling, which was associate with inactivating of EGFR related downstream signalling pathways including AKT, ERK, JNK, and p38 MAPK. Based on this synergy, the conjugates of HCPT and CRI (compounds CH-1 and CH-2) with different chemical bonds were synthesised. Compound CH-1 exhibited stronger cytotoxicity than HCPT and CRI alone or in combination. The combination of HCPT and CRI might be a promising therapeutic regimen and the conjugate CH-1was a potential target drug for the treatment of lung cancer.

Abstract Introduction Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30–60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. Methods and analysis This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6–10 am) or a bedtime (6–10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. Discussion Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. Trial registration ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}

Abstract As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.

Chronic pruritus is a clinical manifestation of a variety of cutaneous and systemic diseases. Persist chronic pruritus leads to a decreased quality of life. Nowadays the efficacy of traditional therapeutic regimens is not satisfactory, and the treatment of chronic pruritus is facing difficulties. Therefore, it is crucial to explore the pathogenesis of chronic pruritus and to develop new therapeutic strategies, including targeted drugs. This review focuses on the interaction between sensory terminals and immune cells in the skin and summarizes the progress on the mechanisms of chronic pruritic diseases such as atopic dermatitis, psoriasis, diabetic pruritus, and chronic pruritus of unknown origin. To elucidate the regulatory role of neuroimmune interaction in cutaneous inflammation and the pathological process of chronic pruritus can facilitate future basic and clinical research.

Summary: Neoblasts are the only cells capable of proliferation in planarians. The traditional flow cytometry protocol using Hoechst inhibits the cell cycle. Here, we present a protocol for culturing and functionally manipulating planarian neoblasts using SiR-DNA-based flow cytometry. We describe steps for cell dissociation and staining, flow cytometry, and cell collection and culture. We then detail procedures for Nanoluciferase mRNA transfection. This protocol facilitates further investigations into the pluripotency and regeneration mechanisms within neoblasts.For complete details on the use and execution of this protocol, please refer to Lei et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson–Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis.

Abstract Background Massive fetomaternal hemorrhage (FMH) is a rare event during pregnancy that may cause severe fetal anemia or death. Case presentation This paper reports two cases of fetomaternal hemorrhage with unexplained reasons. Both cases required emergency caesarean sections for non-reassuring fetal status and were treated with neonatal blood transfusion. Fetomaternal hemorrhage was confirmed via maternal Kleihauer-Betke test. Conclusion We found parenchymal pallor, increased nucleated red blood cells (nRBCs), and syncytial knots (SKs) in the placentas, which are compatible with fetal anemia. Immunohistochemical staining indicated VEGF, CD34, and CD31 expression in the endothelial cells of the capillaries, characteristic of massive FMH placenta. This article also reviews the particular histopathological changes in FHM placenta according to the placental lesion classification system.

The product design process, fraught with uncertainties and ambiguities in its requirements and constraints, commonly traverses multiple stages, each emphasizing distinct design aspects. This engenders heterogeneity in decision-making criteria, rendering the effective integration of information from various stages of product design decision-making (PDDM) a pivotal task in identifying the optimal design solution. Surprisingly, limited research has attended to the challenge of consolidating such heterogeneous information across multiple PDDM stages. To bridge this gap, our study employs real numbers, interval numbers, and linguistic terms to capture the heterogeneous judgments of decision-makers. We fuse the Maximization Deviation Method with the analytic hierarchy process (AHP) for determining indicators’ weights, while decision-makers’ weights are derived through a dual consideration of uncertainty measure using fuzzy entropy and a distance-minimization model applied to the PDDM matrix for achieving consistency. Leveraging the advantage of axiomatic design, product design alternatives are evaluated based on their PDDM information content of PDDM matrices. Given the multistage nature of product design, stages’ weights are computed by assessing the information content and consistency degree of PDDM matrices at each stage. Ultimately, our approach achieves multistage heterogeneous decision-making fusion in product design through information axiom weighting. A case study involving the decision-making process for a specific numerical control machine design illustrates the efficacy of our method in integrating multistage heterogeneous PDDM data, yielding a comprehensive perspective on the viability of product design schemes. Results show that the ranking sequence of the product design schemes solidifies to x3 > x2 > x1 in stages 2 and 3 of PDDM, diverging from the initial order observed in stage 1 (x2 > x3 > x1), while the fused result from the multistage heterogeneous PDDM analysis aligns with the later stages’ rankings, indicating the credibility and persuasiveness are fortified. This methodology thus offers a robust framework for synthesizing and navigating the uncertainties and complexities inherent in multistage heterogeneous PDDM contexts.

RNA is an important information and functional molecule. It can respond to the regulation of life processes and is also a key molecule in gene expression and regulation. Therefore, RNA detection technology has been widely used in many fields, especially in disease diagnosis, medical research, genetic engineering and other fields. However, the current RT-qPCR for RNA detection is complex, costly and requires the support of professional technicians, resulting in it not having great potential for rapid application in the field. PCR-free techniques are the most attractive alternative. They are a low-cost, simple operation method and do not require the support of large instruments, providing a new concept for the development of new RNA detection methods. This article reviews current PCR-free methods, overviews reported RNA biosensors based on electrochemistry, SPR, microfluidics, nanomaterials and CRISPR, and discusses their challenges and future research prospects in RNA detection.

Abstract Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.

Abstract Background This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system. Methods Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine. Results Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P

Abstract Background Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. Methods The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. Results Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. Conclusions Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

IntroductionTo achieve effective conservation objectives, it is crucial to map biodiversity patterns and hotspots while considering multiple influencing factors. However, focusing solely on biodiversity hotspots is inadequate for species conservation on a landscape scale. This emphasizes the importance of integrating hotspots with the home ranges of species to identify priority conservation areas.MethodsCompiling the vegetation data with environmental and anthropogenic disturbance data collected from kilometer-grid plots in Bawangling Nature Reserve, Hainan, China, we analyzed the spatial distribution of plant diversity (species richness and Shannon-Wiener index), as well as the main drivers affecting these patterns. We also investigated the spatial distribution of hotspots using a threshold approach and compared them with the home ranges of the flagship species, Hainan gibbon (Nomascus hainanus).ResultClimate and soil are predominant drivers shaping the spatial pattern of plant diversity in Bawangling Nature Reserve, surpassing the influence of anthropogenic disturbance and topographic factors. Both diversity indices exhibit a generally similar pattern with exceptions in surrounding areas of Futouling and Elongling. The hotspots identified by the Shannon-Wiener index showed a higher spatial overlap with the home ranges of Hainan gibbon compared to the species richness hotspots. The recently established Hainan gibbon Group E in 2019, located 8 km away from the original Futouling habitat, does not coincide with identified hotspots.DiscussionOur findings indicate that the hotspots of plant diversity within the habitat of Hainan gibbon Group E are relatively limited, emphasizing the necessity of giving precedence to its conservation. Integrating hotspots with the home ranges of critically endangered species offers decision-makers valuable information to establish rational conservation networks in the context of changing environments, as well as a reference for habitat restoration of species.

Glutamate receptor-like genes (GLRs) are essential for plant growth and development and for coping with environmental (biological and non-biological) stresses. In this study, 13 GLR members were identified in the Vanilla planifolia genome and attributed to two subgroups (Clade I and Clade III) based on their physical relationships. Cis-acting element analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated the GLR gene regulation’s complexity and their functional diversity. Expression analysis revealed a relatively higher and more general expression pattern of Clade III members compared to the Clade I subgroup in tissues. Most GLRs showed significant differences in expression during Fusarium oxysporum infection. This suggested that GLRs play a critical role in the response of V. planifolia to pathogenic infection. These results provide helpful information for further functional research and crop improvement of VpGLRs.

Glutamate receptor-like genes (GLRs) are essential in the growth and development of plants and many physiological and biochemical processes; however, related information in soybean is lacking. In this study, 105 GLRs, including 67 Glycine soja and 38 Glycine max GLRs, were identified and divided into two clades (Clades II and III) according to their phylogenetic relationships. GLR members in the same branch had a relatively conservative motif composition and genetic structure. Furthermore, the soybean GLR family mainly experienced purification selection during evolution. Cis-acting element analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomic annotations indicated the complexity of the gene regulation and functional diversity of the soybean GLR. Moreover, transcriptome data analysis showed that these GLRs had different expression profiles in different tissues, and Clade III members had higher and more common expression patterns. Additionally, the expression profiles under jasmonic acid treatment and salt stress indicate that the GLR participated in the jasmonic acid signaling pathway and plays a role in salt treatment. This study provides information for a comprehensive understanding of the soybean GLR family and a reference for further functional research and genetic improvement.

BackgroundMental health problems are common among men who have sex with men (MSM) living with HIV and may negatively affect medication adherence. Psychosocial interventions designed to address these urgent needs are scarce in China. Incorporating behavioral health theories into intervention development strengthens the effectiveness of these interventions. The absence of a robust theoretical basis for interventions may also present challenges to identify active intervention ingredients. ObjectiveThis study aims to systematically describe the development of a mobile health–based intervention for MSM recently diagnosed with HIV in China, including the theoretical basis for the content and the considerations for its technological delivery. MethodsWe used intervention mapping (IM) to guide overall intervention development, a behavioral intervention technology model for technological delivery design, and a human-centered design and cultural adaptation model for intervention tailoring throughout all steps of IM. ResultsThe dialectical behavior therapy (DBT)–informed intervention, Turning to Sunshine, comprised 3 components: app-based individual skills learning, group-based skills training, and on-demand phone coaching. The theoretical basis for the intervention content is based on the DBT model of emotions, which fits our conceptualization of the intervention user’s mental health needs. The intervention aims to help MSM recently diagnosed with HIV (1) survive moments of high emotional intensity and strong action urges, (2) change emotional expression to regulate emotions, and (3) reduce emotional vulnerability, as well as (4) augment community resources for mental health services. Technological delivery considerations included rationale of the medium, complexity, and esthetics of information delivery; data logs; data visualization; notifications; and passive data collection. ConclusionsThis study laid out the steps for the development of a DBT-informed mobile health intervention that integrated app-based individual learning, group-based skills training, and phone coaching. This intervention, Turning to Sunshine, aims to improve mental health outcomes for MSM newly diagnosed with HIV in China. The IM framework informed by human-centered design principles and cultural adaptation considerations offered a systematic approach to develop the current intervention and tailor it to the target intervention users. The behavioral intervention technology model facilitated the translation of behavioral intervention strategies into technological delivery components. The systematic development and reporting of the current intervention can serve as a guide for similar intervention studies. The content of the current intervention could be adapted for a broader population with similar emotional struggles to improve their mental health outcomes.

Abstract Loss of TGF-β-mediated growth suppression is a major contributor to the development of cancers, best exemplified by loss-of-function mutations in genes encoding components of the TGF-β signaling pathway in colorectal and pancreatic cancers. Alternatively, gain-of-function oncogene mutations can also disrupt antiproliferative TGF-β signaling. However, the molecular mechanisms underlying oncogene-induced modulation of TGF-β signaling have not been extensively investigated. Here, we show that the oncogenic BCR-ABL1 of chronic myelogenous leukemia (CML) and the cellular ABL1 tyrosine kinases phosphorylate and inactivate Smad4 to block antiproliferative TGF-β signaling. Mechanistically, phosphorylation of Smad4 at Tyr195, Tyr301, and Tyr322 in the linker region interferes with its binding to the transcription co-activator p300/CBP, thereby blocking the ability of Smad4 to activate the expression of cyclin-dependent kinase (CDK) inhibitors and induce cell cycle arrest. In contrast, the inhibition of BCR-ABL1 kinase with Imatinib prevented Smad4 tyrosine phosphorylation and re-sensitized CML cells to TGF-β-induced antiproliferative and pro-apoptotic responses. Furthermore, expression of phosphorylation-site-mutated Y195F/Y301F/Y322F mutant of Smad4 in Smad4-null CML cells enhanced antiproliferative responses to TGF-β, whereas the phosphorylation-mimicking Y195E/Y301E/Y322E mutant interfered with TGF-β signaling and enhanced the in vivo growth of CML cells. These findings demonstrate the direct role of BCR-ABL1 tyrosine kinase in suppressing TGF-β signaling in CML and explain how Imatinib-targeted therapy restored beneficial TGF-β anti-growth responses.

Landslide disasters pose a significant threat, with their highly destructive nature underscoring the critical importance of timely and accurate recognition for effective early warning systems and emergency response efforts. In recent years, substantial advancements have been made in the realm of landslide recognition (LR) based on remote sensing data, leveraging deep learning techniques. However, the intricate and varied environments in which landslides occur often present challenges in detecting subtle changes, especially when relying solely on optical remote sensing images. InSAR (Interferometric Synthetic Aperture Radar) technology emerges as a valuable tool for LR, providing more detailed ground deformation data and enhancing the theoretical foundation. To harness the slow deformation characteristics of landslides, we developed the FCADenseNet model. This model is designed to learn features and patterns within ground deformation data, with a specific focus on improving LR. A noteworthy aspect of our model is the integration of an attention mechanism, which considers various monitoring factors. This holistic approach enables the comprehensive detection of landslide disasters across entire watersheds, providing valuable information on landslide hazards. Our experimental results demonstrate the effectiveness of the FCADenseNet model, with an F1-score of 0.7611, which is 9.53% higher than that of FC_DenseNet. This study substantiates the feasibility and efficacy of combining InSAR with deep learning methods for LR. The insights gained from this research contribute to the advancement of regional landslide geological hazard monitoring, identification, and prevention strategies.

Efficient yet sufficient exploration remains a critical challenge in reinforcement learning (RL), especially for Markov Decision Processes (MDPs) with vast action spaces. Previous approaches have commonly involved projecting the original action space into a latent space or employing environmental action masks to reduce the action possibilities. Nevertheless, these methods often lack interpretability or rely on expert knowledge. In this study, we introduce a novel method for automatically reducing the action space in environments with discrete action spaces while preserving interpretability. The proposed approach learns state-specific masks with a dual purpose: (1) eliminating actions with minimal influence on the MDP and (2) aggregating actions with identical behavioral consequences within the MDP. Specifically, we introduce a novel concept called Bisimulation Metrics on Actions by States (BMAS) to quantify the behavioral consequences of actions within the MDP and design a dedicated mask model to ensure their binary nature. Crucially, we present a practical learning procedure for training the mask model, leveraging transition data collected by any RL policy. Our method is designed to be plug-and-play and adaptable to all RL policies, and to validate its effectiveness, an integration into two prominent RL algorithms, DQN and PPO, is performed. Experimental results obtained from Maze, Atari, and μRTS2 reveal a substantial acceleration in the RL learning process and noteworthy performance improvements facilitated by the introduced approach.

BackgroundPrevious observational studies have shown that a potential relationship between anti-Helicobacter pylori (H. pylori) IgG levels and Myocardial Infarction (MI). Nevertheless, the evidence for the causal inferences remains disputable. To further clarify the relationship between anti-H. pylori IgG levels and MI and explore its pathogenesis, we conducted a Mendelian randomization (MR) analysis.MethodsIn this study, we used two-sample Mendelian Randomization (MR) to assess the causality of anti-H. pylori IgG levels on MI and potential pathogenesis, 12 single nucleotide polymorphisms (SNPs) related to anti-H. pylori IgG levels were obtained from the European Bioinformatics Institute (EBI). Summary data from a large-scale GWAS meta-analysis of MI was utilized as the outcome dataset. Summary data of mediators was obtained from the FinnGen database, the UK Biobank, the EBI database, MRC-IEU database, the International Consortium of Blood Pressure, the Consortium of Within family GWAS. Inverse variance weighted (IVW) analysis under the fixed effect model was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed.ResultsOur study revealed that increases of anti-H. pylori IgG levels were significantly related to an increased risk of MI (OR, 1.104; 95% CI,1.042–1.169; p = 7.084 × 10−4) and decreases in HDL cholesterol levels (β, −0.016; 95% CI, −0.026 to −0.006; p = 2.02 × 10−3). In addition, there was no heterogeneity or pleiotropy in our findings.ConclusionThis two-sample MR analysis revealed the causality of anti-H. pylori IgG levels on MI, which might be explained by lower HDL cholesterol levels. Further research is needed to clarify the results.

AbstractStephania cepharantha Hayata (S. cepharantha) is a common folk medicine herb in China with many therapeutic activities. This study used Illumina sequencing technology to construct a circular chloroplast genome map and compared it with that of other Stephania species. The genome of S. cepharantha is 158,052 bp in length, including a large single-copy region of 88,770 bp, a small single-copy region of 19,760 bp, and two reverse repeat regions of 49,522 bp. The genome encodes eight ribosomal ribonucleic acid (RNA) genes, 37 transfer RNA genes, and 85 protein-coding genes. Nucleotide variation analysis revealed that six highly variable regions of Stephania can be used as potential molecular markers for taxonomic research and evolutionary analysis. This study is the first chloroplast genome report on S. cepharantha, and it provides rich and valuable genetic information for understanding the evolutionary relationships and population inheritance of the species.

Although recent studies show the hypolipidemic effect of Rosa roxburghii, however reported findings are contradictory. Using meta-analysis, we aimed to explore the effect of R. roxburghii on blood lipid levels. An extensive literature search was performed to investigate the effect of R. roxburghii on various lipid indexes. The results showed that R. roxburghii fruit can significantly reduce total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase high-density lipoprotein cholesterol levels. R. roxburghii fruit can therefore be used to regulate blood lipid concentrations and it can be considered a valuable adjuvant therapy for blood lipid control. However, this needs confirmation through additional research.

Abstract White‐coat hypertension (WCH) is associated with increased cardiovascular risks. To investigate the relationship between WCH and left ventricular hypertrophy (LVH), the authors recruited 706 participants who underwent anthropometric measurements, blood laboratory analysis, 24h ambulatory blood pressure monitoring (ABPM), and echocardiography. The authors defined WCH as elevated office BP but normal ABPM over 24h, daytime, and nighttime periods. The authors compared the proportion of LVH between the true normotension (NT) and the WCH population, and further assessed the associations between BP indexes and LVH in the two groups, respectively. The proportion of LVH was significantly higher in the WCH group than in NT participants (19.70% vs. 13.12%, P = .036). In the NT group, 24h SBP, 24h PP, daytime SBP, daytime PP and SD of nighttime SBP were associated with LVH after adjustment for demographic and blood biochemical data (all P

Abstract Background There is limited evidence regarding the relationship between lipid parameters and vascular mechanical characteristics in the normotensive population without diabetes mellitus. The aim of this study was to identify an association between lipid parameters and changes in vascular mechanical characteristics between men and women, and in women before and after menopause. Methods Six hundred-seventy patients who underwent vascular functional testing and who fulfilled the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants were from the Qinghai–Tibet Plateau (Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China; mean altitude: 3860 m). Trained clinical physicians assessed brachial-ankle pulse wave velocity (Ba-PWV) and augmentation index adjusted to a 75-beats-per-minute heart rate (AIx@75). To investigate the relationship between lipid parameters and vascular mechanical characteristics in different sexes and menstrual stages, partial correlation analysis and multiple linear regression were used. Results The 670 participants comprised 445 women (103 post-menopausal). Mean Ba-PWV and AIx@75 were 1315.56 ± 243.41 cm/s and 25.07% ± 15.84%, respectively. Men had greater Ba-PWV values compared with women (1341.61 ± 244.28 vs 1302.39 ± 242.17 cm/s, respectively; P

The host always employs various ways to defend against viral infection and spread. However, viruses have evolved their own effective strategies, such as inhibition of RNA translation of the antiviral effectors, to destroy the host's defense barriers. Protein synthesis, commonly controlled by the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), is a basic cellular biological process among all species. In response to viral infection, in addition to inducing the transcription of antiviral cytokines by innate immunity, infected cells also inhibit the RNA translation of antiviral factors by activating the protein kinase R (PKR)-eIF2α signaling pathway. Regulation of innate immunity has been well studied; however, regulation of the PKR-eIF2α signaling pathway remains unclear. In this study, we found that the E3 ligase TRIM21 negatively regulates the PKR-eIF2α signaling pathway. Mechanistically, TRIM21 interacts with the PKR phosphatase PP1α and promotes K6-linked polyubiquitination of PP1α. Ubiquitinated PP1α augments its interaction with PKR, causing PKR dephosphorylation and subsequent translational inhibition release. Furthermore, TRIM21 can constitutively restrict viral infection by reversing PKR-dependent translational inhibition of various previously known and unknown antiviral factors. Our study highlights a previously undiscovered role of TRIM21 in regulating translation, which will provide new insights into the host antiviral response and novel targets for the treatment of translation-associated diseases in the clinic.

This paper proposes a new cover selection method for steganography. We focus on the scenario that the available images for selection contain diversified sources, i.e., nature images and metaverse images. For the scenario, we design a targeted strategy to evaluate the suitability for steganography of a candidate image, which selects images according to the undetectability against steganalytic tools symmetrically. Firstly, steganalytic features of the candidate images are extracted. Then, the features are fed on a steganalytic classifier, and the possibility of carrying secret data is calculated for cover selection. As a result, the selected images are the best candidates to resist steganalysis. Experimental results show that our method performs better than existing cover selection schemes when checked by steganalytic tools.

Ensuring road safety, structural stability and durability is of paramount importance, and detecting road cracks plays a critical role in achieving these goals. We propose a GM-ResNet-based method to enhance the precision and efficacy of crack detection. Leveraging ResNet-34 as the foundational network for crack image feature extraction, we consider the challenge of insufficient global and local information assimilation within the model. To overcome this, we incorporate the global attention mechanism into the architecture, facilitating comprehensive feature extraction across the channel and the spatial width and height dimensions. This dynamic interaction across these dimensions optimizes feature representation and generalization, resulting in a more precise crack detection outcome. Recognizing the limitations of ResNet-34 in managing intricate data relationships, we replace its fully connected layer with a multilayer fully connected neural network. We fashion a deep network structure by integrating multiple linear, batch normalization and activation function layers. This construction amplifies feature expression, stabilizes training convergence and elevates the performance of the model in complex detection tasks. Moreover, tackling class imbalance is imperative in road crack detection. Introducing the focal loss function as the training loss addresses this challenge head-on, effectively mitigating the adverse impact of class imbalance on model performance. The experimental outcomes on a publicly available crack dataset emphasize the advantages of the GM-ResNet in crack detection accuracy compared to other methods. It is worth noting that the proposed method has better evaluation indicators in the detection results compared with alternative methodologies, highlighting its effectiveness. This validates the potency of our method in achieving optimal crack detection outcomes.

ABSTRACT: Aluminum (Al) is a ubiquitous environmental pollutant representing a significant global health hazard to human and animal health, including chicks. Al toxicity causes oxidative stress, leading to tissue injury, and consequently causes various diseases. NRF2 signaling is vital for protecting cells against oxidative stress. Nuclear xenobiotic receptors are activated by exogenous toxins, thereby inducing the transcription of cytochrome P450 enzyme systems (CYP450s) isoforms involved in xenobiotic metabolism and transport. However, little is known about Al-induced oxidative stress, nuclear xenobiotic receptors and fibrosis in chicks and the mechanisms involved. In this study, male chicks were treated with 0 mg/kg and 500 mg/kg Al2(SO4)3 to evaluate the mechanisms for Al-induced immunotoxicity. Histopathology revealed pathological injury, fibrin aggregation, disruption of the Nuclear Xenobiotic Receptors, and alteration of CYP450s homeostasis in Al-treated chicks due to oxidative stress. Notably, regulation of the NRF2 pathway and CYP450s and fibrosis-related genes was found to play a vital role in inhibiting immunotoxicity. This study provides new insights regarding the mechanisms of Al-induced immunotoxicity, including activation of the nuclear xenobiotic receptors, triggering oxidative stress, and altering the homeostasis of CYP450s in chicks. Further, it provides a theoretical basis for controlling Al exposure and highlights the importance of further studying its mechanisms to provide additional information for formulating preventive measures.

Proximity labeling catalyzed by promiscuous enzymes, such as APEX2, has emerged as a powerful approach to characterize multiprotein complexes and protein–protein interactions. However, current methods depend on the expression of exogenous fusion proteins and cannot be applied to identify proteins surrounding post-translationally modified proteins. To address this limitation, we developed a new method to label proximal proteins of interest by antibody-mediated protein A-ascorbate peroxidase 2 (pA-APEX2) labeling (AMAPEX). In this method, a modified protein is bound in situ by a specific antibody, which then tethers a pA-APEX2 fusion protein. Activation of APEX2 labels the nearby proteins with biotin; the biotinylated proteins are then purified using streptavidin beads and identified by mass spectrometry. We demonstrated the utility of this approach by profiling the proximal proteins of histone modifications including H3K27me3, H3K9me3, H3K4me3, H4K5ac, and H4K12ac, as well as verifying the co-localization of these identified proteins with bait proteins by published ChIP-seq analysis and nucleosome immunoprecipitation. Overall, AMAPEX is an efficient method to identify proteins that are proximal to modified histones.