Chronic stress induces Alzheimer's disease-like pathologies through DNA damage-Chk1-CIP2A signaling.

Stress is an important initiating factor in promoting Alzheimer's disease (AD) pathogenesis. However, the mechanism by which stress induces AD-like cognitive impairment remains to be clarified. Here, we demonstrate that DNA damage is increased in stress hormone Corticotropin-releasing factor (CRF)-treated cells and in brains of mice exposed to chronic restraint stress. Accumulation of DNA damage drives activation of cell cycle checkpoint protein kinase 1 (Chk1), upregulation of cancerous inhibitor of PP2A (CIP2A), tau hyperphosphorylation, and Aß overproduction, eventually resulting in synaptic impairment and cognitive deficits. Pharmacological intervention targeting Chk1 by specific inhibitor and DNA damage by vitamin C, suppress DNA damage-Chk1-CIP2A signaling pathway in chronic stress animal model, which in turn attenuate AD-like pathologies, synaptic impairments and cognitive deficits. Our study uncovers a novel molecular mechanism of stress-induced AD-like pathologies and provides effective preventive and therapeutic strategies targeting this signaling pathway.

Exosomal HSPB1, interacting with FUS protein, suppresses hypoxia-induced ferroptosis in pancreatic cancer by stabilizing Nrf2 mRNA and repressing P450.

Ferroptosis is a new type of programmed cell death, which has been involved in the progression of tumours. However, the regulatory network of ferroptosis in pancreatic cancer is still largely unknown. Here, using datasets from GEO and TCGA, we screened HSPB1, related to the P450 monooxygenase signalling, a fuel of ferroptosis, to be a candidate gene for regulating pancreatic cancer cell ferroptosis. We found that HSPB1 was enriched in the exosomes derived from human pancreatic cancer cell lines SW1990 and Panc-1. Then, hypoxic SW1990 cells were incubated with exosomes alone or together with HSPB1 siRNA (si-HSPB1), and we observed that exosomes promoted cell proliferation and invasion and suppressed ferroptosis, which was reversed by si-HSPB1. Moreover, we found a potential binding affinity between HSPB1 and FUS, verified their protein interaction by using dual-colour fluorescence colocalization and co-IP assays, and demonstrated the promoting effect of FUS on oxidative stress and ferroptosis in hypoxic SW1990 cells. Subsequently, FUS was demonstrated to bind with and stabilize the mRNA of Nrf2, a famous anti-ferroptosis gene that negatively regulates the level of P450. Furthermore, overexpressing FUS and activating the Nrf2/HO-1 pathway (using NK-252) both reversed the inhibitory effect of si-HSPB1 on exosome functions. Finally, our in vivo studies showed that exosome administration promote tumour growth in nude mice of xenotransplantation, which was able to be eliminated by knockdown of HSPB1. In conclusion, exosomal HSPB1 interacts with the RNA binding protein FUS and decreases FUS-mediated stability of Nrf2 mRNA, thus suppressing hypoxia-induced ferroptosis in pancreatic cancer.

Bioinformatics analysis and validation of genes related to paclitaxel's anti-breast cancer effect through immunogenic cell death.

Research indicated that Paclitaxel (PTX) can induce immunogenic cell death (ICD) through immunogenic modulation. However, the combination of PTX and ICD has not been extensively studied in breast cancer (BRCA). The TCGA-BRCA and GSE20685 datasets were enrolled in this study. Samples from the TCGA-BRCA dataset were consistently clustered based on selected immunogenic cell death-related genes (ICD-RGs). Next, candidate genes were obtained by overlapping differentially expressed genes (DEGs) between BRCA and normal groups, intersecting genes common to DEGs between cluster1 and cluster2 and hub module genes, and target genes of PTX from five databases. The univariate Cox algorithm and the least absolute shrinkage and selection operator (LASSO) were performed to obtain biomarkers and build a risk model. Following observing the immune microenvironment in differential risk subgroups, single-gene gene set enrichment analysis (GSEA) was carried out in all biomarkers. Finally, the expression of biomarkers was analyzed. Enrichment analysis showed that 626 intersecting genes were linked with inflammatory response. Further five biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified and a risk model was built. The model's performance was validated using GSE20685 dataset. Furthermore, the biomarkers were enriched with adaptive immune response. Lastly, the experimental results indicated that the alterations in IL18, SH2D2A, and CHI3L1 expression after treatment matched those in the public database. In this study, Five PTX-ICD-related biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified to aid in predicting BRCA treatment outcomes.

Tau induces inflammasome activation and microgliosis through acetylating NLRP3.

BACKGROUND: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. METHODS: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. RESULTS: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. CONCLUSIONS: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.

Effect of Li6.4La3Zr1.4Ta0.6O12 Fillers on the Interfacial Properties between Composite PEO-LiTFSI Electrolytes with Li Metal during Cycling.

PEO-LiX solid polymer electrolyte (SPE) with the addition of Li6.4La3Zr1.4Ta0.6O12 (LLZTO) fillers is considered as a promising solid-state electrolyte for solid-state Li-ion batteries. However, the developments of the SPE have caused additional challenges, such as poor contact interface and SPE/Li interface stability during cycling, which always lead to potentially catastrophic battery failure. The main problem is that the real impact of LLZTO fillers on the interfacial properties between SPE and Li metal is still unclear. Herein, we combined the electrochemical measurement and in situ synchrotron-based X-ray absorption near-edge structure (XANES) imaging technology to study the role of LLZTO fillers in directing SPE/Li interface electrochemical performance. In situ XRF-XANES mapping during cycling showed that addition of an appropriate amount of LLZTO fillers (50 wt %) can improve the interfacial contact and stability between SPE and Li metal without reacting with the PEO and Li salts. Additionally, it also demonstrated the beneficial effect of LLZTO particles for suppressing the interface reactions between the Li metal and PEO-LiTFSI SPE and further inhibiting Li-metal dendrite growth. The Li|LiFePO4 batteries deliver long cycling for over 700 cycles with a low-capacity fade rate of 0.08% per cycle at a rate of 0.3C, revealing tremendous potential in promoting the large-scale application of future solid-state Li-ion batteries.

Advances and Challenges in Electrolyte Development for Magnesium-Sulfur Batteries: A Comprehensive Review.

Magnesium-sulfur batteries are an emerging technology. With their elevated theoretical energy density, enhanced safety, and cost-efficiency, they have the ability to transform the energy storage market. This review investigates the obstacles and progress made in the field of electrolytes which are especially designed for magnesium-sulfur batteries. The primary focus of the review lies in identifying electrolytes that can facilitate the reversible electroplating and stripping of Mg2+ ions whilst maintaining compatibility with sulfur cathodes and other battery components. The review also addresses the critical issue of managing the shuttle effect on soluble magnesium polysulfide by looking at the innovative engineering methods used at the sulfur cathode's interface and in the microstructure design, both of which can enhance the reaction kinetics and overall battery efficiency. This review emphasizes the significance of reaction mechanism analysis from the recent studies on magnesium-sulfur batteries. Through analysis of the insights proposed in the latest literature, this review identifies the gaps in the current research and suggests future directions which can enhance the electrochemical performance of Mg-S batteries. Our analysis highlights the importance of innovative electrolyte solutions and provides a deeper understanding of the reaction mechanisms in order to overcome the existing barriers and pave the way for the practical application of Mg-S battery technology.

The Urinary Metabolome of Newborns with Perinatal Complications.

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual's entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

Adsorption Dynamics of Uremic Toxins to Novel Modified Magnetic Nanoparticles.

Kidney dysfunction leads to the retention of metabolites in the blood compartment, some of which reach toxic levels. Uremic toxins are associated with the progression of kidney disease and other symptoms of kidney failure (i.e., nausea, itchiness, and hypertension). Toxin removal ameliorates symptoms and reduces further organ damage, but membrane-based methods are inadequate for this purpose. Engineered adsorbents may facilitate enhanced removal of retained toxins, especially those bound strongly by proteins. Poly 2-(methacryloyloxy)ethyl phosphorylcholine-co-ß-cyclodextrin (p(MPC-co-PMßCD)) coated magnetic nanoparticles are synthesized, characterized for their physicochemical properties (Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), thermogravimetric analysis(TGA), gel permeation chromatography (GPC), and transmission electron microscope (TEM), and evaluated toxin adsorption from a complex solution for the first time to quantify the effects of film chemistry and incubation time on the adsorbed toxinome (the collection of toxins). Uremic toxins are bound by even "low-fouling" polymer films themselves; providing further insight into how small molecule interactions with "low-fouling" films may affect protein-surface interactions. These results suggest a dynamic interaction between toxins and surfaces that is not driven by solution concentration alone. This knowledge will help advance the design of novel adsorbent films for clearing uremic toxins.

Myoglobin improves doxycycline sensitivity in pancreatic cancer through promoting heme oxygenase-1-mediated ferroptosis.

Ferroptosis is expected to be a therapeutic target for cancers including pancreatic cancer. We aimed to screen genes that regulate ferroptosis and doxycycline resistance in pancreatic cancer and to explore the underlying mechanisms. Bioinformatics analysis was performed to identify genes that respond to ferroptosis in two human pancreatic cancer cells with GOT1 knocked down or not. 325 and 842 genes were upregulated in MiaPaCa and Tu8902 cells in response to GOT1 knockdown, with 43 genes shared. Among the 43 genes, 14 genes were identified to interact with ferroptosis key genes. MB and HMOX1 were the genes most sensitive to Erastin and doxycycline. Moreover, MB and HMOX1 expression was higher in human normal pancreatic duct epithelial cells than in pancreatic cancer cells. MB and HMOX1 proteins physically bound and promoted each other's expression. By interacting with HMOX1, MB suppressed pancreatic cancer cell proliferation, colony formation and invasion, and promoted cell ferroptosis and sensitivity to erastin and doxycycline. Silencing HMOX1 reversed the promoting effect of MB on cell ferroptosis and sensitivity to doxycycline. A pancreatic cancer xenograft model was established by subcutaneous injection of Panc-1 cells transfected with or without Ad-MB, and doxycycline was administered intraperitoneally. Overexpression of MB enhanced the inhibitory effect of doxycycline on xenograft growth. In conclusion, MB facilitated doxycycline sensitivity in pancreatic cancer cells through promoting HMOX1-mediated ferroptosis.

Ultrasound image segmentation based on Transformer and U-Net with joint loss.

Background: Ultrasound image segmentation is challenging due to the low signal-to-noise ratio and poor quality of ultrasound images. With deep learning advancements, convolutional neural networks (CNNs) have been widely used for ultrasound image segmentation. However, due to the intrinsic locality of convolutional operations and the varying shapes of segmentation objects, segmentation methods based on CNNs still face challenges with accuracy and generalization. In addition, Transformer is a network architecture with self-attention mechanisms that performs well in the field of computer vision. Based on the characteristics of Transformer and CNNs, we propose a hybrid architecture based on Transformer and U-Net with joint loss for ultrasound image segmentation, referred to as TU-Net. Methods: TU-Net is based on the encoder-decoder architecture and includes encoder, parallel attention mechanism and decoder modules. The encoder module is responsible for reducing dimensions and capturing different levels of feature information from ultrasound images; the parallel attention mechanism is responsible for capturing global and multiscale local feature information; and the decoder module is responsible for gradually recovering dimensions and delineating the boundaries of the segmentation target. Additionally, we adopt joint loss to optimize learning and improve segmentation accuracy. We use experiments on datasets of two types of ultrasound images to verify the proposed architecture. We use the Dice scores, precision, recall, Hausdorff distance (HD) and average symmetric surface distance (ASD) as evaluation metrics for segmentation performance. Results: For the brachia plexus and fetal head ultrasound image datasets, TU-Net achieves mean Dice scores of 79.59% and 97.94%; precisions of 81.25% and 98.18%; recalls of 80.19% and 97.72%; HDs (mm) of 12.44 and 6.93; and ASDs (mm) of 4.29 and 2.97, respectively. Compared with those of the other six segmentation algorithms, the mean values of TU-Net increased by approximately 3.41%, 2.62%, 3.74%, 36.40% and 31.96% for the Dice score, precision, recall, HD and ASD, respectively.

Novel Ca-Chelating Peptides from Protein Hydrolysate of Antarctic Krill (Euphausia superba): Preparation, Characterization, and Calcium Absorption Efficiency in Caco-2 Cell Monolayer Model.

Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.

Obeticholic acid alleviates intrauterine growth restriction induced by di-ethyl-hexyl phthalate in pregnant female mice by improving bile acid disorder.

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. Intrahepatic cholestasis of pregnancy (ICP), distinguished by maternal pruritus and elevated serum bile acid levels, is linked to unfavorable pregnancy consequences. Few studies have investigated the potential effect of gestational DEHP exposure on the cholestasis in pregnant female mice, and the underlying mechanisms remain unclear. In the present study, a mouse model of cholestasis during pregnancy was established by DEHP exposure. We found that DEHP induces elevated bile acid levels by affecting bile acid synthesis and transporter receptor expression in the maternal liver and placenta of pregnant female mice, ultimately leading to intrauterine growth restriction (IUGR). In addition, DEHP changed the bile acid composition of maternal serum and liver as well as placenta and amniotic fluid in pregnant female mice; Importantly, we found that DEHP down-regulates the expression of farnesoid X receptor (FXR), which is considered to be a bile acid receptor. FXR agonist obeticholic acid (OCA) effectively alleviated the adverse effects of DEHP on pregnant female mice. While, OCA itself had no adverse effects on normal pregnant female mice. In summary, DEHP could induces bile acid disorder and IUGR in pregnant female mice by affect FXR, which was reversed by OCA.

Advances in Optical Probes for the Detection of Hydrazine in Environmental and Biological Systems.

Hydrazine, as a crucial raw material in the fine chemical industry, plays an indispensable role in fuel, catalyst, pesticide and drug synthesis. Due to its good water solubility and high toxicity, hydrazine can cause irreparable damage to water and soil in the environment, and it can also be released by taking certain drugs, which brings potential risks to human health. Therefore, it is vital to develop a method that can specifically detect hydrazine in the environment and in vivo. As an effective analysis and detection tool, fluorescence probe has attracted extensive attention in recent years. In this review, we summarized and classified hydrazine fluorescence probes based on various reaction mechanisms, and discussed their structures and applications in the past ten years. At least, we briefly outline the challenges and prospects in this field.

The effect of the modified fat-protein unit algorithm compared with that of carbohydrate counting on postprandial glucose in adults with type-1 diabetes when consuming meals with differing macronutrient compositions: a randomized crossover trial.

BACKGROUND: The optimization of glucose control in type-1 diabetes is challenged by postprandial glycemic variability. This study aimed to compare the postprandial glycemic effects of carbohydrate counting and the modified fat-protein unit (FPU) algorithms following meals with different protein and fat emphases in adults with type-1 diabetes. METHODS: Thirty adults with type-1 diabetes aged 18 to 45 years participated in a randomized crossover trial. In a random order, participants consumed four test meals with equivalent energy and different macronutrient emphases on four separate mornings. The modified FPU algorithms and carbohydrate counting were used to determine the insulin dose for the test meals. A continuous glucose monitoring system was used to measured postprandial glycemia. RESULTS: Compared with carbohydrate counting, the modified FPU algorithm significantly decreased the late postprandial mean glucose levels (p = 0.026) in high protein-fat meals. The number of hypoglycemia episodes was similar between insulin dosing algorithms for the high protein-fat meals; hypoglycemic events were considerably higher for the modified FPU in the normal protein-fat meal (p = 0.042). CONCLUSIONS: The modified FPU algorithm may improve postprandial glycemic control after consuming high protein-fat meals in adults with type-1 diabetes but may result in increased hypoglycemia risk when used with a normal protein-fat meal.

Pyrolytic mechanisms of typical organic components of sewage sludge in the presence of CaO: Polysaccharides, proteins, and lipids.

The addition of CaO could facilitate the conversion of sewage sludge (SS) from waste to high-purity syngas. The pyrolytic characteristics of SS are a comprehensive manifestation of polysaccharides, proteins, and lipids, while the influence of CaO on their pyrolytic characteristics is rarely reported. This study conducted a thorough investigation into the pyrolytic mechanism of starch, protein, and lipid in the presence of CaO by analysing their thermal behavior, gaseous products, liquid tar, and residual char. The findings from TGA, GC, GC-MS, and FT-IR analysis indicate that the addition of CaO catalytically lowers the pyrolysis temperature of starch, protein, and lipid components and promotes their conversion into small molecules, resulting in increased syngas production. Moreover, the combination of char with the carbonation and calcination cycle of CaO leads to a significant boost in syngas (H2 and CO) yield, with up to 3 and 10 times increase from starch and protein, respectively, and a higher syngas selectivity of up to 65 %. The study also identifies those polysaccharides and proteins are the primary sources of syngas. This study can provide further insight into SS pyrolysis for syngas production in the presence of CaO and the necessary parameters to predict the pyrolysis behavior of SS in industrial applications.

[Retracted] Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar­to­ductal metaplasia through PI3K/Akt/IKK.

Following the publication of the above article, a concerned reader drew to the Editor's attention that there were a number of apparent anomalies associated with the western blots featured in Figs. 1C and E, 3A, C and E, 4A, C and E, 5B, 8A and C; moreover, the images shown for the immunohistochemical experiments in Fig. 8E contained groupings of cells that were markedly similar in appearance, comparing across the eight separate figure parts. After having conducted an internal investigation of the data in this paper, the Editor of International Journal of Molecular Medicine has judged that the potentially anomalous presentation of the western blotting data and the strikingly similar groupings of cells in Fig. 8E were too extensive that these features could have been attributed to pure coincidence. Therefore, the Editor has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for bringing this matter to our attention. [International Journal of Molecular Medicine 35: 653­663, 2015; DOI: 10.3892/ijmm.2014.2055].

Epidemiological analysis and risk prediction of scrub typhus from 2006 to 2021 in Sichuan, China.

Background: In the past decade, the number of reported cases of scrub typhus (ST) has increased dramatically in Sichuan Province. We aimed to overview the epidemiological characteristics of ST, identify the variables contributing to the spatial distribution, and estimate the risk areas of ST occurrence. Methods: Daily ST cases reported at the county level from 2006 to 2021 and datasets on environmental and socioeconomic variables were obtained. Joinpoint regression model was utilized to examine the incidence trends and to calculate the annual percentage change. Global spatial autocorrelation analysis was employed to explore the spatial temporal patterns. Then BRT model was employed to identify variables that make sense and predict the risk areas of ST occurrence. Result: It has been reported that there were 6,338 ST cases in Sichuan Province from 2006 to 2021, and the incidence rates continued to rise. Most cases were distributed between June and October each year, peaking in August. During the study period, the cases showed spatial clustering at the county level, mainly in the Panxi area, and then slowly spread to the northwest and northeast. Shrubs, precipitation, farmland and maximum temperature were the primary variables that affected the spatial distribution of this disease. It was estimated that the areas including Liangshan, Panzhihua, Bazhong, and Guangyuan were most at risk of transmission. and there were approximately 32.315 million people living in the areas with potential risk of infection throughout Sichuan. Conclusion: Many counties in Sichuan Province were estimated to be susceptible to ST. Our found in this data-driven study could be used to guide the implementation of targeted prevention and control measures in high-risk areas.

ArhGAP11A mediates amyloid-ß generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-ß (Aß) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aß generation and Aß oligomer (Aßo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aß generation by decreasing the expression of APP, PS1, and ß-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aßo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aß production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aßos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.

[Corrigendum] Role of the EZH2/miR­200 axis in STAT3­mediated OSCC invasion.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Figs. 7A and 8A. apparently the same mouse had been featured to represent two different experimental groups, albeit displaying distinct fluorescence values. Moreover, following an independent investigation in the Editorial Office, an additional instance of probable data duplication was also noted, comparing between the 'SCC15 / si­NC' cell migration image in Fig. 2D and the 'SCC15­EV' migration assay image in Fig. 1C. After having consulted their original data, the authors realized that these errors arose during the process of assembling the images for Figs. 2 and 8. First, the image for the DZNep (42d) experiment in Fig. 7A had inadvertently been used for the mimic NC (7d) experiment in Fig. 8A; moreover, the 'SCC15 / si­NC' cell migration image in Fig. 2D had been selected incorrectly. The revised versions of Figs. 2 and 8, showing the correct data for the the 'SCC15 / si­NC' cell migration image in Fig. 2D and the mimic NC (7d) experiment in Fig. 8A, are shown on the next two pages. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 52: 1149­1164, 2018; DOI: 10.3892/ijo.2018.4293].

Microglia activation mediates circadian rhythm disruption-induced cognitive impairment in mice.

Alzheimer's disease (AD) is the leading cause of dementia and there are no effective treatments for this disease currently. Circadian rhythm disruption (CRD) is a hallmark of modern society that appears to be on the rise. It is well reported that AD is associated with disrupted circadian functioning and CRD can impair cognitive function. However, the cellular mechanisms underlying CRD-associated cognitive decline remain elusive. In this study, we investigated whether microglia are involved in CRD-induced cognitive decline. We established experimental 'jet lag' (phase delay of the light/dark cycles)-induced CRD mouse model and observed significant impairment of spatial learning and memory function in these mice. In the brain, CRD resulted in neuroinflammation, which was characterized by microglia activation and increased pro-inflammatory cytokine production, impairments in neurogenesis and reduction of synaptic proteins in the hippocampus. Interestingly, elimination of microglia with the colony stimulating factor-1 receptor inhibitor PLX3397 prevented CRD-induced neuroinflammation, cognitive decline, impairment of neurogenesis and loss of synaptic proteins. These findings collectively suggest that microglia activation plays a key role in CRD-induced cognitive deficit most likely through neuroinflammation-mediated impairments in adult neurogenesis and synapses.