USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

Deubiquitinating enzymes (DUBs) regulate antiviral immune response through targeting DNA sensor signaling pathway members. As one of the DNA sensors, interferon (IFN)-γ inducible protein 16 (IFI16) play a major role in response to virus infections through activating the canonical STING/TBK-1/IRF3 signaling pathway. Only a few studies discuss the function of DUBs in IFI16-mediated antiviral response. Ubiquitin-specific protease 12 (USP12), which is one of the major members of the USP family, participates in various biological functions. However, whether USP12 regulates the nucleic acid sensor to modulate antiviral immune responses has not yet been elucidated. In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-ß, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs). Moreover, USP12 deficiency increased HSV-1 replication and host susceptibility to HSV-1 infection. Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling. Overall, our findings demonstrate an essential role of USP12 in DNA-sensing signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

[This corrects the article DOI: 10.1371/journal.ppat.1011480.].

Role of the GLP2-Wnt1 axis in silicon-rich alkaline mineral water maintaining intestinal epithelium regeneration in piglets under early-life stress.

Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2-Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/ß-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5+ ISC cell cycle passage through the G1-S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP23-33) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2-Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2-Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI.

Rare Earth-Carbon Dots Nanocomposite-Modified Glass Nanopipettes: Electro-Optical Detection of Bacterial ppGpp.

As an important alarmone nucleotide, guanosine 3'-diphosphate-5'-diphosphate (ppGpp) can regulate the survival of bacteria under strict environmental conditions. Direct detection of ppGpp in bacteria with high sensitivity and selectivity is crucial for elucidating the role of ppGpp in bacterial stringent response. Herein, the terbium-carbon dots nanocomposite (CDs-Tb) modified glass nanopipet was developed for the recognition of ppGpp. The CDs-Tb in glass nanopipette preserved their fluorescence properties as well as the coordination capacity of Tb3+ toward ppGpp. The addition of ppGpp not only led to the fluorescence response of CDs-Tb but also triggered variations of surface charge inside the glass nanopipet, resulting in the ionic current response. Compared with nucleotides with similar structures, this method displayed good selectivity toward ppGpp. Moreover, the dual signals (fluorescence and ionic current) offered a built-in correction for potential interference. Apart from the high selectivity, the proposed method can determine the concentration of ppGpp from 10-13 to 10-7 M. Taking advantage of the significant analytical performance, we monitored ppGpp in Escherichia coli under different nutritional conditions and studied the relationship between ppGpp and DNA repair, which is helpful for overcoming antibiotic resistance and promoting the development of potential drugs for antibacterial treatment.

The GA and ABA signaling is required for hydrogen-mediated seed germination in wax gourd.

BACKGROUND: Hydrogen gas (H2), a novel and beneficial gaseous molecule, plays a significant role in plant growth and development processes. Hydrogen-rich water (HRW) is regarded as a safe and easily available way to study the physiological effects of H2 on plants. Several recent research has shown that HRW attenuates stress-induced seed germination inhibition; however, the underlying modes of HRW on seed germination remain obscure under non-stress condition. RESULTS: In this current study, we investigated the possible roles of gibberellin (GA) and abscisic acid (ABA) in HRW-regulated seed germination in wax gourd (Benincasa hispida) through pharmacological, physiological, and transcriptome approaches. The results showed that HRW application at an optimal dose (50% HRW) significantly promoted seed germination and shortened the average germination time (AGT). Subsequent results suggested that 50% HRW treatment stimulated GA production by regulating GA biosynthesis genes (BhiGA3ox, BhiGA2ox, and BhiKAO), whereas it had no effect on the content of ABA and the expression of its biosynthesis (BhiNCED6) and catabolism genes (BhiCYP707A2) but decreased the expression of ABA receptor gene (BhiPYL). In addition, inhibition of GA production by paclobutrazol (PAC) could block the HRW-mediated germination. Treatment with ABA could hinder HRW-mediated seed germination and the ABA biosynthesis inhibitor sodium tungstate (ST) could recover the function of HRW. Furthermore, RNA-seq analysis revealed that, in the presence of GA or ABA, an abundance of genes involved in GA, ABA, and ethylene signal sensing and transduction might involve in HRW-regulated germination. CONCLUSIONS: This study portrays insights into the mechanism of HRW-mediated seed germination, suggesting that HRW can regulate the balance between GA and ABA to mediate seed germination through ethylene signals in wax gourd.

Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

Dissecting the genetic basis of Fusarium crown rot resistance in wheat by genome wide association study.

KEY MESSAGE: A locus conferring Fusarium crown rot resistance was identified on chromosome arm 3DL through genome wide association study and further validated in two recombinant inbred lines populations. Fusarium crown rot (FCR) is a severe soil borne disease in many wheat growing regions of the world. In this study, we attempted to detect loci conferring FCR resistance through a new seedling inoculation assay. A total of 223 wheat accessions from different geography origins were used to assemble an association panel for GWAS analysis. Four genotypes including Heng 4332, Luwanmai, Pingan 998 and Yannong 24 showed stable resistance to FCR. A total of 54 SNPs associated with FCR resistance were identified. Among the 10 putative QTLs represented by these SNPs, seven QTLs on chromosome 2B, 3A, 3D, 4A, 7A and 7B were novel and were consistently detected in at least two of the three trials conducted. Qfcr.cau.3D-3, which was targeted by 38 SNPs clustered within a genomic region of approximately 5.57 Mb (609.12-614.69 Mb) on chromosome arm 3DL, was consistently detected in all the three trials. The effects of Qfcr.cau.3D-3 were further validated in two recombinant inbred line populations. The presence of this locus reduced FCR severity up to 21.55%. Interestingly, the collinear positions of sequences containing the four SNPs associated with two FCR loci (Qfcr.cau.3A and Qfcr.cau.3B) were within the regions of Qfcr.cau.3D-3, suggesting that genes underlying these three loci may be homologous. Our results provide useful information for improving FCR resistance in wheat.

A novel QTL conferring Fusarium crown rot resistance on chromosome 2A in a wheat EMS mutant.

KEY MESSAGE: A novel QTL on chromosome 2A for Fusarium crown rot resistance was identified and validated in wheat. Fusarium crown rot (FCR) is a fungal disease that causes significant yield losses in many cereal growing regions in the world. In this study, genetic analysis was conducted for a wheat EMS mutant C549 which showed stable resistance to FCR at seedling stage. A total of 10 QTL were detected on chromosomes 1A, 2A, 3B, 4A, 6B, and 7B using a population of 138 F7 recombinant inbred lines (RILs) derived from a cross between C549 and a Chinese germplasm 3642. A novel locus Qfcr.cau-2A, which accounted for up to 24.42% of the phenotypic variation with a LOD value of 12.78, was consistently detected across all six trials conducted. Furthermore, possible effects of heading date (HD) and plant height on FCR severity were also investigated in the mapping population. While plant height had no effects on FCR resistance, a weak and negative association between FCR resistance and HD was observed. A QTL for HD (Qhd.cau-2A.2) was coincident with Qfcr.cau-2A. Conditional QTL mapping indicated that although Qfcr.cau-2A and Qhd.cau-2A.2 had significant interactions, Qfcr.cau-2A remained significant after the effects of HD was removed. It is unlikely that genes underlying these two loci are same. Nevertheless, the stable expression of Qfcr.cau-2A in the validation population of 148 F7 RILs developed between C549 and its wild parent Chuannong 16 demonstrated the potential value of this locus in FCR resistance breeding programs.

Prediction of survival and analysis of prognostic factors for patients with AFP negative hepatocellular carcinoma: a population-based study.

PURPOSE: Hepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency. PATIENTS AND METHODS: Data from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model. RESULTS: This study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752-0.772) and 0.752 (95% CI: 0.740-0.769) for predicting OS, and 0.785 (95% CI: 0.774-0.795) and 0.779 (95% CI: 0.762-0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging. CONCLUSION: The age(HR:1.012, 95% CI: 1.006-1.018, P-value < 0.001), ethnicity(African-American: HR:0.946, 95% CI: 0.783-1.212, P-value: 0.66; Others: HR:0.737, 95% CI: 0.613-0.887, P-value: 0.001), tumor diameter(HR:1.006, 95% CI: 1.004-1.008, P-value < 0.001), year of diagnosis (HR:0.852, 95% CI: 0.729-0.997, P-value: 0.046), tumor grade(Grade 2: HR:1.124, 95% CI: 0.953-1.326, P-value: 0.164; Grade 3: HR:1.984, 95% CI: 1.574-2.501, P-value < 0.001; Grade 4: HR:2.119, 95% CI: 1.115-4.027, P-value: 0.022), surgery(Liver Resection: HR:0.193, 95% CI: 0.160-0.234, P-value < 0.001; Liver Transplant: HR:0.102, 95% CI: 0.072-0.145, P-value < 0.001), chemotherapy(HR:0.561, 95% CI: 0.471-0.668, P-value < 0.001), and radiotherapy(HR:0.641, 95% CI: 0.463-0.887, P-value:0.007) were independent prognostic factors for patients with ANHC. We developed a nomogram model for predicting the OS and CSS of patients with ANHC, with a good predictive performance.

Temperature dependence of carbon metabolism in the leaves in sun and shade in a subtropical forest.

Rising temperatures pose a threat to the stability of climate regulation by carbon metabolism in subtropical forests. Although the effects of temperature on leaf carbon metabolism traits in sun-exposed leaves are well understood, there is limited knowledge about its impacts on shade leaves and the implications for ecosystem-climate feedbacks. In this study, we measured temperature response curves of photosynthesis and respiration for 62 woody species in summer (including both evergreen and deciduous species) and 20 evergreen species in winter. The aim was to uncover the temperature dependence of carbon metabolism in both sun and shade leaves in subtropical forests. Our findings reveal that shade had no significant effects on the mean optimum photosynthetic temperatures (TOpt) or temperature range (T90). However, there were decreases observed in mean stomatal conductance, mean area-based photosynthetic rates at TOpt and 25 °C, as well as mean area-based dark respiration rates at 25 °C in both evergreen and deciduous species. Moreover, the respiration-temperature sensitivity (Q10) of sun leaves was higher than that of shade leaves in winter, with the reverse being true in summer. Leaf economics spectrum traits, such as leaf mass per area, and leaf concentration of nitrogen and phosphorus across species, proved to be good predictors of TOpt, T90, mass-based photosynthetic rate at TOpt, and mass-based photosynthetic and respiration rate at 25 °C. However, Q10 was poorly predicted by these leaf economics spectrum traits except for shade leaves in winter. Our results suggest that model estimates of carbon metabolism in multilayered subtropical forest canopies do not necessitate independent parameterization of T90 and TOpt temperature responses in sun and shade leaves. Nevertheless, a deeper understanding and quantification of canopy variations in Q10 responses to temperature are necessary to confirm the generality of temperature-carbon metabolism trait responses and enhance ecosystem model estimates of carbon dynamics under future climate warming.

Obesity and lipid indices as predictors of depressive symptoms in middle-aged and elderly Chinese: insights from a nationwide cohort study.

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.

Obesity-and lipid-related indices as a risk factor of hypertension in mid-aged and elderly Chinese: a cross-sectional study.

OBJECTIVE: Hypertension refers to the persistent elevation of blood pressure above the established normal range, resulting in increased pressure exerted by blood on the walls of blood vessels during its circulation. Recent studies have identified significant associations between obesity and lipid-related indices, as well as hypertension. Nevertheless, these studies have yet to comprehensively examine the correlation between the two variables. Our objective is to identify the fat and lipid-related indices that have the strongest correlation with hypertension. METHOD: There was a total of 9488 elderly and middle-aged Chinese citizens who participated in this investigation. The participants in this research were separated into distinct gender cohorts. The participants were classified into normal and hypertensive categories according to their gender, with hypertension defined as a blood pressure level of 140/90 mmHg or higher, or a history of hypertension. Through the utilization of binary logistic regression analyses and the receiver operator curve (ROC), the optimal among fourteen indicators associated with obesity and lipids were identified. RESULTS: After adjusting for variables, statistical analysis showed that all 14 measures of obesity and lipid were risk factors for hypertension. The receiver operating characteristic (ROC) curve analysis reveals that the Chinese visceral adiposity index (CVAI) has the highest degree of relationship to hypertension. Simultaneously, a statistically significant association between hypertension and these 14 variables was observed in both males and females. CONCLUSION: There was a significant independent association between various parameters related to obesity and lipid-related index and the presence of hypertension, indicating that these factors can be considered risk factors for hypertension. CVAI and WHtR (waist height ratio) can be used to screen the high-risk groups of hypertensions in middle-aged and elderly people in China, and then take individualized health care measures to reduce the harm of hypertension.

Identification of anthropogenic source of Pb and Cd within two tropical seagrass species in South China: Insight from Pb and Cd isotopes.

Seagrass beds are susceptible to deterioration and heavy metals represent a crucial impact factor. The accumulation of heavy metal in two tropical seagrass species were studied in South China in this study and multiple methods were used to identify the heavy metal sources. E. acoroides (Enhalus acoroides) and T. hemperichii (Thalassia hemperichii) belong to the genus of Enhalus and Thalassia in the Hydrocharitaceae family, respectively. Heavy metal concentrations in the two seagrasses followed the order of Cr > Zn > Cu > Ni > As > Pb > Co > Cd based on the whole plant, and their bioconcentration factors were 31.8 ± 29.3 (Cr), 5.7 ± 1.3 (Zn), 7.0 ± 3.8 (Cu), 3.0 ± 1.9 (Ni), 1.2 ± 0.3 (As), 1.7 ± 0.9 (Pb), 9.1 ± 11.1 (Co) and 2.8 ± 0.6 (Cd), indicating the intense enrichment in Co and Cr within the two seagrasses. The two seagrasses were prone to accumulate all the listed heavy metals (except for As in E. acoroides), especially Co (BCFs of 1124) and Cr (BCFs of 2689) in the aboveground parts, and the belowground parts of both seagrasses also accumulated most metals (BCFs of 27) excluding Co and Pb. The Pb isotopic ratios (mean 208Pb/204Pb, 207Pb/204Pb and 206Pb/204Pb values of 38.2054, 15.5000 and 18.3240, respectively) and Cd isotopic compositions (δ114/110Cd values ranging from -0.09‰ to 0.58‰) within seagrasses indicated the anthropogenic sources of Pb and Cd including coal combustion, traffic emissions and agricultural activities. This study described the absorption characteristics of E. acoroides and T. hemperichii to some heavy metals, and further demonstrated the successful utilization of Pb and Cd isotopes as discerning markers to trace anthropogenic origins of heavy metals (mainly Pb and Cd) in seagrasses. Pb and Cd isotopes can mutually verify and be helpful to understand more information in pollution sources and improve the reliability of conclusion deduced from concentrations or a single isotope.

The ROS/SIRT1/STAR axis as a target for melatonin ameliorating atrazine-induced mitochondrial dysfunction and steroid disorders in granulosa cells.

The granulosa cells (GCs) of birds are essential for the reproduction and maintenance of populations in nature. Atrazine (ATR) is a potent endocrine disruptor that can interfere with reproductive function in females and Diaminochlorotriazine (DACT) is the primary metabolite of ATR in the organism. Melatonin (MT) is an endogenous hormone with antioxidant properties that plays a crucial role in development of animal germ cells. However, how ATR causes mitochondrial dysfunction, abnormal secretion of steroid hormones, and whether MT prevents ATR-induced female reproductive toxicity remains unclear. Thus, the purpose of this study is to investigate the protective effect of MT against ATR-induced female reproduction. In the present study, the GCs of quail were divided into 6 groups, as follows: C (Serum-free medium), MT (10 µM MT), A250 (250 µM ATR), MA250 (10 µM MT+250 µM ATR), D200 (200 µM DACT) and MD200 (10 µM MT+200 µM DACT), and were cultured for 24 h. The results revealed that ATR prevented GCs proliferation and decreased cell differentiation. ATR caused oxidative damage and mitochondrial dysfunction, leading to disruption of steroid synthesis, which posed a severe risk to GC's function. However, MT supplements reversed these changes. Mechanistically, our study exhibited that the ROS/SIRT1/STAR axis as a target for MT to ameliorate ATR-induced mitochondrial dysfunction and steroid disorders in GCs, which provides new insights into the role of MT in ATR-induced reproductive capacity and species conservation in birds.

The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Improved YOLOv8-Based Target Precision Detection Algorithm for Train Wheel Tread Defects.

Train wheels are crucial components for ensuring the safety of trains. The accurate and fast identification of wheel tread defects is necessary for the timely maintenance of wheels, which is essential for achieving the premise of conditional repair. Image-based detection methods are commonly used for detecting tread defects, but they still have issues with the misdetection of water stains and the leaking of small defects. In this paper, we address the challenges posed by the detection of wheel tread defects by proposing improvements to the YOLOv8 model. Firstly, the impact of water stains on tread defect detection is avoided by optimising the structure of the detection layer. Secondly, an improved SPPCSPC module is introduced to enhance the detection of small targets. Finally, the SIoU loss function is used to accelerate the convergence speed of the network, which ensures defect recognition accuracy with high operational efficiency. Validation was performed on the constructed tread defect dataset. The results demonstrate that the enhanced YOLOv8 model in this paper outperforms the original network and significantly improves the tread defect detection indexes. The average precision, accuracy, and recall reached 96.95%, 96.30%, and 95.31%.

FR-PatchCore: An Industrial Anomaly Detection Method for Improving Generalization.

In recent years, a multitude of self-supervised anomaly detection algorithms have been proposed. Among them, PatchCore has emerged as one of the state-of-the-art methods on the widely used MVTec AD benchmark due to its efficient detection capabilities and cost-saving advantages in terms of labeled data. However, we have identified that the PatchCore similarity principal approach faces significant limitations in accurately locating anomalies when there are positional relationships between similar samples, such as rotation, flipping, or misaligned pixels. In real-world industrial scenarios, it is common for samples of the same class to be found in different positions. To address this challenge comprehensively, we introduce Feature-Level Registration PatchCore (FR-PatchCore), which serves as an extension of the PatchCore method. FR-PatchCore constructs a feature matrix that is extracted into the memory bank and continually updated using the optimal negative cosine similarity loss. Extensive evaluations conducted on the MVTec AD benchmark demonstrate that FR-PatchCore achieves an impressive image-level anomaly detection AUROC score of up to 98.81%. Additionally, we propose a novel method for computing the mask threshold that enables the model to scientifically determine the optimal threshold and accurately partition anomalous masks. Our results highlight not only the high generalizability but also substantial potential for industrial anomaly detection offered by FR-PatchCore.

Advancing Ultrasonic Defect Detection in High-Speed Wheels via UT-YOLO.

In the context of defect detection in high-speed railway train wheels, particularly in ultrasonic-testing B-scan images characterized by their small size and complexity, the need for a robust solution is paramount. The proposed algorithm, UT-YOLO, was meticulously designed to address the specific challenges presented by these images. UT-YOLO enhances its learning capacity, accuracy in detecting small targets, and overall processing speed by adopting optimized convolutional layers, a special layer design, and an attention mechanism. This algorithm exhibits superior performance on high-speed railway wheel UT datasets, indicating its potential. Crucially, UT-YOLO meets real-time processing requirements, positioning it as a practical solution for the dynamic and high-speed environment of railway inspections. In experimental evaluations, UT-YOLO exhibited good performance in best recall, mAP@0.5 and mAP@0.5:0.95 increased by 37%, 36%, and 43%, respectively; and its speed also met the needs of real-time performance. Moreover, an ultrasonic defect detection data set based on real wheels was created, and this research has been applied in actual scenarios and has helped to greatly improve manual detection efficiency.

Graphene Oxide-Mediated Regulation of Volume Exclusion and Wettability in Biomimetic Phosphorylation-Responsive Ionic Gates.

Replicating phosphorylation-responsive ionic gates via artificial fluidic systems is essential for biomolecular detection and cellular communication research. However, current approaches to governing the gates primarily rely on volume exclusion or surface charge modulation. To overcome this limitation and enhance ion transport controllability, we introduce graphene oxide (GO) into nanochannel systems, simultaneously regulating the volume exclusion and wettability. Moreover, inspired by (cAMP)-dependent protein kinase A (PKA)-regulated L-type Ca2+ channels, we employ peptides for phosphorylation which preserves them as nanoadhesives to coat nanochannels with GO. The coating boosts steric hindrance and diminishes wettability, creating a substantial ion conduction barrier, which represents a significant advancement in achieving precise ion transport regulation in abiotic nanochannels. Leveraging the mechanism, we also fabricated a sensitive biosensor for PKA activity detection and inhibition exploration. The combined regulation of volume exclusion and wettability offers an appealing strategy for controlled nanofluidic manipulation with promising biomedical applications in diagnosis and drug discovery.