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Ischemic colitis (IC) is a serious but underrecognized complication potentially associated with bowel preparation. While previous studies have reported sporadic cases, the true frequency and drug-specific associations remain unclear. This study evaluates the association between oral bowel cleansers and IC using real-world pharmacovigilance data. We conducted a disproportionality analysis using 20 years of data (2004-2024) from the FDA Adverse Event Reporting System (FAERS). IC cases linked to bisacodyl, polyethylene glycol (PEG), and oral sulfate solution (OSS) were identified. Multivariate logistic regression was applied to explore factors associated with IC and serious clinical outcomes. Among 43,958 adverse event reports related to bowel cleansers, 75 cases of IC were identified. Bisacodyl showed the strongest disproportionality signal for IC (reporting odds ratio (ROR) = 237.25), with a reporting proportion of 7.9%, followed by PEG (ROR = 2.18) and OSS (ROR = 3.64). Older age (≥70 years) and cardiovascular comorbidities were associated with more severe outcomes, such as hospitalization and death. Notably, reports of IC associated with PEG included six fatal and three life-threatening events. To our knowledge, this is one of the largest pharmacovigilance analyses exploring ischemic colitis associated with bowel preparation agents. The findings raise concerns about the presumed safety of PEG and reveal a strong disproportionality signal for bisacodyl. These results highlight the need for individualized bowel preparation strategies, especially in elderly patients with comorbidities.

Sign language (SL) has strong structural features. Various gestures and the complex trajectories of hand movements bring challenges to sign language recognition (SLR). Based on the inherent correlation between gesture and trajectory of SL action, SLR is organically divided into gesture-based recognition and gesture-related movement trajectory recognition. One hundred and twenty commonly used Chinese SL words involving 9 gestures and 8 movement trajectories, are selected as research and test objects. The method based on the amplitude state of surface electromyography (sEMG) signal and acceleration signal is used for vocabulary segmentation. The multi-sensor decision fusion method of coupled hidden Markov model is used to complete the recognition of SL vocabulary, and the average recognition rate is 90.41%. Experiments show that the method of sEMG signal and motion information fusion has good practicability in SLR.

Background Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-β-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown. Methods Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining. Results The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1β/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm. Conclusions Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH.

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18–59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p <0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL.

Various antibiotics have been used in the treatment of cancers, via their anti-proliferative, pro-apoptotic and anti-epithelial-mesenchymal-transition (EMT) capabilities. However, increasingly studies have indicated that antibiotics may also induce cancer generation by disrupting intestinal microbiota, which further promotes chronic inflammation, alters normal tissue metabolism, leads to genotoxicity and weakens the immune response to bacterial malnutrition, thereby adversely impacting cancer treatment. Despite the advent of high-throughput sequencing technology in recent years, the potential adverse effects of antibiotics on cancer treatments via causing microbial imbalance has been largely ignored. In this review, we discuss the double-edged sword of antibiotics in the field of cancer treatments, explore their potential mechanisms and provide solutions to reduce the potential negative effects of antibiotics.

The effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only in isolated case reports and small series. This paper aims to review the current evidence regarding rituximab (RTX) use in the treatment of ILD related to anti-MDA5 DM (anti-MDA5 DM-ILD). We conducted a review by searching PubMed, Web of Science, Embase, and Cochrane for articles with information on patients with anti-MDA5 DM and RTX treatment, published until August 2021, in English language. The selected studies listed variation in chest high-resolution computed tomography (HRCT) and/or pulmonary function test (PFT) as a primary outcome, in patients with anti-MDA5 DM-related ILD after using RTX. Of the 145 potentially eligible articles, 17 were selected. The information gathered from a total of 35 patients with anti-MDA5 DM-ILD was reviewed, including 13 men and 22 women. Patient age at onset was 47.60 ± 13.72 years old. A total of 11.43% (4/35) of the patients were found to have chronic ILD (C-ILD) and 88.57% (31/30) exhibited rapidly progressive ILD (RP-ILD). Most patients (29/30) had typical DM rashes. Prior to RTX administration, the majority of patients (27/35) were treated with medium- or high-dose glucocorticoids and at least one additional immunotherapeutic agent. With regard to RTX efficacy for ILD in anti-MDA5 DM, 71.43% (25/35) of the patients responded to treatment. Skin rash also improved in more than half of the patients after RTX treatment. The most common side effects were infections, reported by 37.14% (13/35) of the patients after using RTX. As a CD20 targeting drug, RTX is a promising therapeutic tool for anti-MDA5 DM-ILD, although the risk of infections should be considered before treatment. Further prospective controlled studies are required to evaluate the optimal RTX treatment regimen. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289714, identifier CRD42021289714.

Human hexokinase 2 is an essential regulator of glycolysis that couples metabolic and proliferative activities in cancer cells. The binding of hexokinase 2 to the outer membrane of mitochondria is critical for its oncogenic activity. However, the regulation of hexokinase 2 binding to mitochondria remains unclear. Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492. SUMO-specific protease SENP1 mediates the de-SUMOylation of hexokinase 2. SUMO-defective hexokinase 2 preferably binds to mitochondria and enhances both glucose consumption and lactate production and decreases mitochondrial respiration in parallel. This metabolic reprogramming supports prostate cancer cell proliferation and protects cells from chemotherapy-induced cell apoptosis. Moreover, we demonstrate an inverse relationship between SENP1-hexokinase 2 axis and chemotherapy response in prostate cancer samples. Our data provide evidence for a previously uncovered posttranslational modification of hexokinase 2 in cancer cells, suggesting a potentially actionable strategy for preventing chemotherapy resistance in prostate cancer. The oncogenic activity of Hexokinase 2, the first rate-limiting enzyme of glycolysis, requires its mitochondrial localization. Here, the authors show that SUMOylation of hexokinase 2 disrupts its binding to mitochondria and protects cells from tumorigenesis in prostate cancer.

Neuroinflammation is initiated in response to ischemic stroke, and is usually characterized by microglial activation and polarization. Stimulator of interferon genes (STING) has been shown to play a critical role in anti-tumor immunity and inflammatory diseases. Nevertheless, the effect and underlying mechanisms of STING on microglial polarization after ischemic stroke remain unclarified. In this study, acute ischemic stroke was simulated using a model of middle cerebral artery occlusion (MCAO) at adult male C57BL/6 mice in vivo and the BV2 microglia oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro . The specific STING inhibitor C-176 was administered intraperitoneally at 30min after MCAO. We found that the expression of microglial STING was increased following MCAO and OGD/R. Pharmacologic inhibition of STING with C-176 reduced the ischemia/reperfusion (I/R)-induced brain infarction, edema and neuronal injury. Moreover, blockade of STING improved neurological performance and cognitive function and attenuated neuronal degeneration in the hippocampus after MCAO. Mechanistically, both in vivo and in vitro , we delineated that STING could promote the polarization of microglia towards the M1 phenotype and restrain M2 microglia polarization via downstream pathways, including interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB). In addition, mitochondrial DNA (mtDNA), which is released to microglial cytoplasm induced by I/R injury, could facilitate microglia towards M1 modality through STING signaling pathway. Treatment with C-176 abolished the detrimental effects of mtDNA on stroke outcomes. Taken together, these findings suggest that STING, activated by mtDNA, could polarize microglia to the M1 phenotype following MCAO. Inhibition of STING may serve as a potential therapeutic strategy to mitigate neuroinflammation after ischemic stroke.

Land transformation during global urbanization has led to a sharp decrease in farmland, causing not only food security issues but also ecological problems. To address this issue, the Chinese government has implemented the Requisition–Compensation Balance Policy for Farmland (RCBF) in 1997. This policy effectively curbed the reduction of farmland, but the compensated land often comes from mountainous and desert areas, leading to fragmentation of farmland and subsequent ecological security issues. The balance between farmland requisition and compensation is closely related to ecological security. However, current research on farmland occupation and compensation is mostly based on farmland area. The area occupied and compensated for by farmland in different regions is inconsistent, and using only net increase or decrease in area to represent farmland occupation and compensation cannot accurately and fairly compare the degree of farmland occupation and compensation between regions. Therefore, this study has proposed a novel index to measure the balance of farmland requisition and compensation—the Farmland Requisition and Compensation Index (FOCI). FOCI can transform dimensional expressions that represent the area of farmland occupation and compensation into dimensionless expressions, namely scalars, which makes it possible to visually and fairly compare the degree of farmland occupation in each region. Then, this new index has been used to investigate the spatiotemporal evolution of farmland requisition and compensation in China at the national and provincial levels over the past 30 years (1990–2021), as well as the impact of this change on the fragmentation of farmland landscape and ecological service value. The results indicate that (1) FOCI shows a trend of first decreasing and then increasing at both national and provincial scales; (2) Provinces with increasing FOCI are mainly concentrated in the southeast and northwest regions, while significant decreases in FOCI are observed in the southwest region, indicating a shift of the FOCI center of gravity towards the southeast; (3) FOCI and farmland landscape fragmentation are significantly positively correlated spatially, suggesting that provinces with higher levels of farmland requisition and compensation also exhibit higher levels of farmland landscape fragmentation; (4) FOCI and ecological service value are significantly negatively correlated spatially, indicating that provinces with higher levels of farmland requisition and compensation have lower ecological service values, with these areas mainly concentrated in the northwest region of China. In general, FOCI has the advantage of eliminating the dimensional influence in different regions and could be a reliable alternative for evaluating the balance of farmland requisition and compensation between regions.

Decoding semantic concepts for imagination and perception tasks (SCIP) is important for rehabilitation medicine as well as cognitive neuroscience. Electroencephalogram (EEG) is commonly used in the relevant fields, because it is a low-cost noninvasive technique with high temporal resolution. However, as EEG signals contain a high noise level resulting in a low signal-to-noise ratio, it makes decoding EEG-based semantic concepts for imagination and perception tasks (SCIP-EEG) challenging. Currently, neural network algorithms such as CNN, RNN, and LSTM have almost reached their limits in EEG signal decoding due to their own short-comings. The emergence of transformer methods has improved the classification performance of neural networks for EEG signals. However, the transformer model has a large parameter set and high complexity, which is not conducive to the application of BCI. EEG signals have high spatial correlation. The relationship between signals from different electrodes is more complex. Capsule neural networks can effectively model the spatial relationship between electrodes through vector representation and a dynamic routing mechanism. Therefore, it achieves more accurate feature extraction and classification. This paper proposes a spatio-temporal capsule network with a self-correlation routing mechaninsm for the classification of semantic conceptual EEG signals. By improving the feature extraction and routing mechanism, the model is able to more effectively capture the highly variable spatio-temporal features from EEG signals and establish connections between capsules, thereby enhancing classification accuracy and model efficiency. The performance of the proposed model was validated using the publicly accessible semantic concept dataset for imagined and perceived tasks from Bath University. Our model achieved average accuracies of 94.9%, 93.3%, and 78.4% in the three sensory modalities (pictorial, orthographic, and audio), respectively. The overall average accuracy across the three sensory modalities is 88.9%. Compared to existing advanced algorithms, the proposed model achieved state-of-the-art performance, significantly improving classification accuracy. Additionally, the proposed model is more stable and efficient, making it a better decoding solution for SCIP-EEG decoding.