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The Gaussian noise distribution is typically used in dynamic state estimation (DSE) but it is not always true in practice because of abnormal system inputs, impulsive noise and measurement outliers. In this paper, a new robust DSE approach based on a new robust Lp norm based estimator and the cubature Kalman filter (CKF) is developed for power systems with non-Gaussian noise statistics. The Lp norm based estimator is derived from the Lp norm formula and the quadratic formula in order to alleviate the impacts from bad data and outliers. The proposed Lp-CKF DSE approach exhibits good accuracy because a new estimation error covariance is obtained by using the influence function. The robustness of the proposed Lp-CKF DSE approach is verified by performing simulations on a generator in the IEEE 39-bus system.

Abstract Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI). Here, we proposed a deep unrolled neural network, dubbed as LSFP-Net, for real-time i-MRI reconstruction. By integrating LSFP-Net and a custom-designed, MR-compatible interventional device into a 3 T MRI scanner, a real-time MRI-guided brain intervention system is proposed. The performance of the system was evaluated using phantom and cadaver studies. 2D/3D real-time i-MRI was achieved with temporal resolutions of 80/732.8 ms, latencies of 0.4/3.66 s including data communication, processing and reconstruction time, and in-plane spatial resolution of 1 × 1 mm2. The results demonstrated that the proposed method enables real-time monitoring of the remote-controlled brain intervention, and showed the potential to be readily integrated into diagnostic scanners for image-guided neurosurgery.

The Public-Private Partnership (PPP) is one of the crucial ways to promote the advancement of the Urban Rail Transit Project However, investing in such projects exposes social capital to tremendous risks. To analyze and assess the investment risk of social capital (IRSC), this study utilized the system dynamics (SD) approach to construct an investment risk model. Subsequently, combined with the practical project’s information, the investment risk was assessed, and the impact of boundary risks on the different risk subsystems was analyzed. The results demonstrate the following: (1) the investment risk system comprises three risk subsystems, namely, operating cost, operating revenue, and government subsidy. Among them, the subsidy risk subsystem most significantly influences the IRSC. (2) Of the boundary risks, the design risk and the contractual risk are the most vital factors in preventing and controlling the IRSC. (3) Differences exist in the boundary risks that most affect the regulation of the three risk subsystems. These findings can help social capital determine risk changes and effectively mitigate investment risk. This ability can further attract added social capital into such projects to facilitate the sustainable development of urban infrastructure.

Intestinal disease is a group of complex digestive system diseases imposing a significant burden globally. Identifying the risk factors and potential complications of intestinal disease is important for its prevention and treatment. However, traditional observational clinical studies are limited by confounding factors and reverse causation, making causal inference challenging. Mendelian randomisation (MR) method has been developed to effectively mitigate these constraints and assess the causal relationships. This review briefly introduces the MR method, summarises MR research on intestinal disease and delineates the prospective avenues for future research. Conventional risk factors, such as lifestyle behaviours (eg, physical activity, smoking and alcohol consumption), nutrients (eg, selenium), obesity markers (eg, body mass index and waist-to-hip ratio) and inflammatory biomarkers, have been validated in MR studies. Multiomics MR studies are becoming novel hotspots, which provide a theoretical foundation for the exploration of pathogenesis and the investigation of new drug targets. However, most of the recent studies are based on European individuals, and thus it is necessary to replicate the results in other ancestries. Moreover, triangulation integrating MR and other epidemiology methods is suggested as a validated paradigm for causal inference in future MR studies.

Summary: Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

Abstract Background As the most common type of glaucoma, the etiology of primary open-angle glaucoma (POAG) has not been unified. Autophagy may affect the occurrence and development of POAG, while the specific mechanism and target need to be further explored. Methods The GSE27276 dataset from the Gene Expression Omnibus (GEO) database and the autophagy gene set from the GeneCards database were selected to screen differentially expressed autophagy-related genes (DEARGs) of POAG. Hub DEARGs were selected by constructing protein-protein interaction (PPI) networks and utilizing GSE138125 dataset. Subsequently, immune cell infiltration analysis, genome-wide association study (GWAS) analysis, gene set enrichment analysis (GSEA) and other analyses were performed on the hub genes. Eventually, animal experiments were performed to verify the mRNA levels of the hub genes by quantitative real time polymerase chain reaction (qRT-PCR). Results A total of 67 DEARGs and 2 hub DEARGs, HSPA8 and RPL15, were selected. The hub genes were closely related to the level of immune cell infiltration. GWAS analysis confirmed that the causative regions of the 2 hub genes in glaucoma were on chromosome 11 and chromosome 3, respectively. GSEA illustrated that pathways enriched for highly expressed HSPA8 and RPL15 contained immunity, autophagy, gene expression and energy metabolism-related pathways. qRT-PCR confirmed that the expression of Hspa8 and Rpl15 in the rat POAG model was consistent with the results of bioinformatics analysis. Conclusions This study indicated that HSPA8 and RPL15 may affect the progression of POAG by regulating autophagy and provided new ideas for the pathogenesis and treatment of POAG.

This study aims to investigate the response of Salmonella Newport to plasma-activated water (PAW), a novel disinfectant that attracts attention due to its broad-spectrum antimicrobial efficacy and eco-friendliness. In this work, we demonstrated that S. Newport of different sequence types (STs) could be induced into the viable but nonculturable (VBNC) state by PAW treatment. Notably, a remarkable 99.96% of S. Newport ST45 strain entered the VBNC state after a 12-min PAW treatment, which was the fastest observed among the five S. Newport STs (ST31, ST45, ST46, ST166, ST2364). Secretion of outer membrane vesicles was observed in ST45, suggesting a potential strategy against PAW treatment. Genes related to oxidative stress (sodA, katE, trxA), outer membrane proteins (ompA, ompC, ompD, ompF) and virulence (pagC, sipC, sopE2) were upregulated in the PAW-treated S. Newport, especially in ST45. A reduction of 38–65% in intracellular ATP level after PAW treatment was observed, indicating a contributor to the formation of the VBNC state. In addition, a rapid method for detecting the proportion of VBNC cells in food products based on pagC was established. This study contributes to understanding the formation mechanism of the VBNC state in S. Newport under PAW stress and offers insights for controlling microbial risks in the food industry.

Summary: Background: Mitochondrial dysfunction has been linked to the development of inflammatory bowel disease (IBD), but the genetic pathophysiology was not fully elucidated. We employed Mendelian randomization and colocalization analyses to investigate the associations between mitochondrial-related genes and IBD via integrating multi-omics. Methods: Summary-level data of mitochondrial gene methylation, expression and protein abundance levels were obtained from corresponding methylation, expression and protein quantitative trait loci studies, respectively. We obtained genetic associations with IBD and its two subtypes from the Inflammatory Bowel Disease Genetics Consortium (discovery), the UK Biobank (replication), and the FinnGen study (replication). We performed summary-data-based Mendelian randomization analysis to assess the associations of mitochondrial gene-related molecular features with IBD. Colocalization analysis was further conducted to assess whether the identified signal pairs shared a causal genetic variant. Findings: After integrating the multi-omics data between mQTL-eQTL and eQTL-pQTL, we identified two mitochondrial genes, i.e., PARK7 and ACADM, with tier 1 evidence for their associations with IBD and ulcerative colitis (UC). PDK1 and FISI genes were associated with UC risk with tier 2 and tier 3 evidence, respectively. The methylation of cg05467918 in ACADM was associated with lower expression of ACADM, which fits with the positive effect of cg05467918 methylation on UC risk. Consistently, the inverse associations between gene methylation and gene expression were also observed in PARK7 (cg10385390) and PDK1 (cg17679246), which were corroborated with the protective role in UC. At circulating protein level, genetically predicted higher levels of PARK7 (OR 0.36, 95% CI 0.25–0.52) and HINT1 (OR 0.47, 95% CI 0.30–0.74) were inversely associated with IBD risk; genetically predicted higher level of HINT1 was associated with a decreased risk of Crohn's disease (CD) (OR 0.26, 95% CI 0.14–0.49) and a higher level of ACADM (OR 0.67, 95% CI 0.55–0.83), PDK1 (OR 0.63, 95% CI 0.49–0.81), FIS1 (OR 0.63, 95% CI 0.47–0.83) was associated with a decreased risk of UC. Interpretation: We found that the mitochondrial PARK7 gene was putatively associated with IBD risk, and mitochondrial FIS1, PDK1, and ACADM genes were associated with UC risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to IBD, which may enhance the understanding of the pathogenic mechanisms of IBD development. Funding: XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and Healthy Zhejiang One Million People Cohort (K-20230085).

Abstract The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.

Background: Beverage consumption was found to be associated with cardiovascular disease and mortality in the general population. However, it is unclear whether this association still exists in individuals with inflammatory bowel disease (IBD). Objectives: To investigate the associations of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with cardiovascular disease and all-cause mortality among individuals with IBD. Design: Prospective cohort study. Methods: We included 1981 participants with IBD in the UK Biobank. Consumption of beverages was measured using a validated 24-h diet recall. Outcomes of interest were overall cardiovascular disease and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals (CIs). Results: During a mean (SD) follow-up of 10.1 (1.7) years, we documented 205 cardiovascular events and 133 deaths. Compared to non-consumers, those consuming sugar-sweetened beverages more than 1 unit/day (reported in glasses/cans/250 ml/cartons) were associated with 64% (95% CI: 5–155, p = 0.030) and 97% (95% CI: 16–233, p = 0.012) increased risk of cardiovascular disease and all-cause mortality, respectively. We also observed a 78% (95% CI: 3–205, p = 0.038) increased risk of cardiovascular disease in participants who consumed artificially sweetened beverages more than 1 unit/day when compared with non-consumers. We did not observe significant associations between natural juice consumption and the two outcomes in IBD. Conclusion: Higher sugar- and artificially sweetened beverage consumption were associated with adverse cardiovascular and mortality outcomes in IBD. These exploratory results were consistent with the evidence in the general population and highlighted the importance of diet management in individuals with IBD.

The distribution of measurement noise is usually assumed to be Gaussian in the optimal phasor measurement unit (PMU) placement (OPP) problem. However, this is not always accurate in practice. This paper proposes a new OPP method for smart grids in which the effects of conventional measurements, limited channels of PMUs, zero-injection buses (ZIBs), single PMU loss contingency, state estimation error (SEE), and the maximum SEE variance (MSEEV) are considered. The SEE and MSEEV are both obtained using a robust $t$-distribution maximum likelihood estimator (MLE) because $t$-distribution is more flexible for modeling both Gaussian and non-Gaussian noises. The A- and G-optimal experimental criteria are utilized to form the SEE and MSEEV constraints. This allows the optimization problem to be converted into a linear objective function subject to linear matrix inequality observability constraints. The performance of the proposed OPP method is verified by the simulations of the IEEE 14-bus, 30-bus, and 118-bus systems as well as the 188-bus practical distribution system in China.

Abstract Background The sensitivity of RT-PCR in diagnosing COVID-19 is only 60–70%, and chest CT plays an indispensable role in the auxiliary diagnosis of COVID-19 pneumonia, but the results of CT imaging are highly dependent on professional radiologists. Aims This study aimed to develop a deep learning model to assist radiologists in detecting COVID-19 pneumonia. Methods The total study population was 437. The training dataset contained 26,477, 2468, and 8104 CT images of normal, CAP, and COVID-19, respectively. The validation dataset contained 14,076, 1028, and 3376 CT images of normal, CAP, and COVID-19 patients, respectively. The test set included 51 normal cases, 28 CAP patients, and 51 COVID-19 patients. We designed and trained a deep learning model to recognize normal, CAP, and COVID-19 patients based on U-Net and ResNet-50. Moreover, the diagnoses of the deep learning model were compared with different levels of radiologists. Results In the test set, the sensitivity of the deep learning model in diagnosing normal cases, CAP, and COVID-19 patients was 98.03%, 89.28%, and 92.15%, respectively. The diagnostic accuracy of the deep learning model was 93.84%. In the validation set, the accuracy was 92.86%, which was better than that of two novice doctors (86.73% and 87.75%) and almost equal to that of two experts (94.90% and 93.88%). The AI model performed significantly better than all four radiologists in terms of time consumption (35 min vs. 75 min, 93 min, 79 min, and 82 min). Conclusion The AI model we obtained had strong decision-making ability, which could potentially assist doctors in detecting COVID-19 pneumonia.

Liver cancer is a common malignant tumor known for its difficult treatment and poor prognosis. As a traditional Chinese medicine prescription, Aitongxiao prescription (ATXP) has been used in clinical treatment of primary liver cancer (PLC) for more than ten years, and its therapeutic effect is obvious and has been verified over time. However, the mechanism of ATXP in treating PLC has not been fully elucidated. This study aimed to detect the liver-protective effect of ATXP on a PLC rat model and explore its potential mechanism from the perspective of plasma extracellular vesicle miRNAs. Fifty SPF male SD rats were randomly selected, with six rats as the control group, and the remaining rats were injected with DEN to establish a primary liver cancer model. The model rats were randomly divided into the model group and the ATXP group. After 4 weeks of intervention, the liver-protective effect of ATXP was evaluated using plasma biochemical indicators and histopathological methods. Plasma extracellular vesicles were isolated and extracted, and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Significant differentially expressed miRNAs in extracellular vesicles were screened by Illumina sequencing to explore the therapeutic targets of ATXP and conduct functional analysis. The results showed that ATXP significantly reduced plasma liver function in PLC rats and alleviated liver pathological damage. In addition, plasma extracellular vesicles were isolated and identified. According to the results of GO and KEGG analysis, they were related to multiple biological processes and covered multiple signaling pathways (PI3K-Akt and MAPK signaling pathways, etc.). The interaction between miR-199a-3p and MAP3K4 was determined by bioinformatics methods and dual-luciferase reporter gene detection, confirming that MAP3K4 is the target gene of miR-199a-3p. In conclusion, ATXP protects the liver from DEN-induced PLC, which may be related to the regulation of plasma extracellular vesicle miR-199a-3p. This study further reveals the mechanism of ATXP in treating liver cancer and provides a theoretical basis for subsequent research.

Background: Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases. Methods: Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption. Results: Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn’s disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation. Conclusions: This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases. Funding: The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.

Abstract Objective Cognitive behavioral therapy (CBT) is now included in the treatment of patients with inflammatory bowel disease (IBD) in many settings. However, different clinical trials report different outcomes without consensus. This study aims to evaluate the impact of CBT on the mental state, quality of life and disease activity of patients with IBD. Design Systematic review. Methods This systematic review searched eligible studies from 1946 to December 8, 2019, in MEDLINE, EMBASE, CINAHL, Cochrane library, ClinicalTrials.gov, PsycINFO, Web of Science for eligible randomized controlled trials (RCT). Results Among the initial identified 1807 references, 11 studies met inclusion criteria. CBT was shown to improve patient's quality of life and reduce the level of depression and anxiety post-intervention but was not sustained. Evidence is not enough for the effect of CBT on disease activity, or C-reactive protein level. Conclusions CBT has shown short-term positive psychological effects on IBD patients, but there is insufficient evidence for sustained physical and psychological improvements of IBD patients. PROSPERO registration: CRD42019152330.

Background: Social well-being of patients with inflammatory bowel disease (IBD) is garnering increased attention; however, the impact of social isolation remained poorly understood. Objectives: We investigated the joint association of social isolation and IBD with premature deaths to articulate the profound impact of social isolation in IBD prognosis. Design: Longitudinal cohort study. Methods: We leveraged data of 486,014 participants from UK Biobank (including 5791 with IBD), the mean follow-up was 11.84 years. Diagnoses of IBD and its subtypes of Crohn’s disease (CD) and ulcerative colitis were confirmed with the combination of self-reporting, primary care, and hospital admission data. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Mortality was ascertained through data linkage with national death registries. Multivariable Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). Results: Comparing non-isolated non-IBD population, the HRs of mortality in patients with IBD who were socially isolated or not were 2.06 (95% CI: 1.69, 2.51) and 1.33 (95% CI: 1.21, 1.45), respectively. The excess risk of death was observed in socially isolated patients with IBD (HR = 1.69, 95% CI: 1.36, 2.11), particularly among patients with CD (HR = 2.06, 95% CI: 1.48, 2.87) than their non-isolated counterparts. Data from subgroup and sensitivity analyses were consistent with those from the primary analysis. Conclusion: Socially isolated patients with IBD especially CD increases the risk of premature death. Preventing social isolation might be a promising approach to improve IBD prognosis. Plain language summary Social isolation as a risk factor to excess mortality in patients with IBD: findings from a longitudinal cohort study Social isolation is prevalent in individuals with inflammatory bowel disease (IBD); however, its potential health impact on IBD prognosis has not been quantitatively well examined. In this study, we explored the association between social isolation and subsequent death, with the focus on patients with IBD. We leveraged data of 486,014 participants (including 5791 with IBD) from UK Biobank. We measured social isolation by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. We ascertained patients with IBD and mortality by self-report data and data linkage with primary care, hospital, and national death registry. Participants were followed up for a mean of 11.84 years. Comparing non-isolated non-IBD population, we found that patients with IBD who were deemed as socially isolated or not were associated with a 2.06-fold (1.69–2.51) and 1.33-fold (1.21–1.45) risk of death, respectively. Furthermore, we revealed that socially isolated patients with IBD and subtype Crohn’s disease (CD) had 69% (36–111%) and 106% (48–187%) increased risk of premature death compared with their non-isolated counterparts, respectively. Social isolation merits attention in IBD care and management. Patients with IBD, especially CD, are more likely to be affected when socially isolated. Targeted social support strategies ought to be devised to improve IBD prognosis.

GRAPHICAL ABSTRACT

In 2021, the price of silica fume had fallen to 400 RMB/ton in some areas, while that of cement had risen to 650 RMB/ton, which provided a realistic basis for applying silica fume in low- and medium-strength concrete. In this paper, the effects of adding a small amount of silica fume on the water demand, setting time, exothermic heat of hydration, fluidity, mechanical properties, and water absorption of mortar with 0.5%, 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of silica fume were investigated respectively. XRD and TG-DTG were used for microscopic analysis. The results showed that silica fume improved the fluidity of the cement fly ash system and reduced the water demand of the cement fly ash system, and that the water demand of the paste was reduced by about 4.5%. Therefore, water or superplasticizers could be reduced while maintaining the same fluidity. The exotherm peak during the hydration reaction are reduced. The silica fume improved the later strength of the specimen, accompanied by a slight decrease in the early strength. The water absorption was significantly reduced. Silica fume consumed CH in the cement-fly ash system and promoted the production of C-S-H. Therefore, the cost of cement consumption and improve performance could be lowered by replacing cement with silica fume.

In this work, spontaneously fermented and inoculation-fermented Akebia trifoliata fruit Jiaosu (SFAJ/IFAJ) were compared. The key metabolites and antioxidant activities of SFAJ and IFAJ were tracked and tested during fermentation. The antioxidant effect of fermented Akebia trifoliata fruit and the underlying mechanisms were explored using network pharmacology for the prediction and verification of the molecular targets and pathways of the Akebia trifoliata fruit’s action against oxidative stress. Furthermore, the results were verified by molecular docking and then investigated, based on a HepG2 cell model. The results of correlation analysis and principal component analysis (PCA) showed that there were significant positive correlations between the phenols, flavonoids, and terpenoids in SFAJ and IFAJ and their antioxidant activities. Network pharmacology and molecular docking analysis disclosed the antioxidation mechanism at the molecular level. In addition, both SFAJ and IFAJ were effective at alleviating oxidative stress in HepG2 cells. In particular, IFAJ performed better than SFAJ in protecting cells with an intracellular reactive oxygen species (ROS) level of 99.96 ± 4.07 U/mg prot, superoxide dismutase (SOD) activity of 41.56 ± 0.06 U/mg prot, catalase (CAT) activity of 91.78 ± 3.85 U/mg prot, and glutathione peroxidase (GSH-Px) activity of 39.32 ± 2.75 mU/mg prot in the IFAJ group. Collectively, this study revealed the changes in bioactive metabolite contents and the in vitro antioxidant activity during fermentation and investigated the protectiveness of SFAJ and IFAJ against oxidative stress within HepG2 cells, promoting the study of the antioxidant efficacy of IFAJ, thereby providing valuable reference data for the optimization of its preparation and the development of relevant products with health benefits.

Summary: Background: Whether meat consumption is related to risk of mortality in patients with inflammatory bowel disease (IBD) remains poorly understood. Methods: In the UK Biobank, 5763 patients with IBD were recruited from 2007 to 2010 and finished a brief food frequency questionnaire at baseline. We followed them until March 13, 2021 to document all-cause death events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause mortality associated with consumptions of fish, unprocessed poultry, unprocessed red meat, and processed meat among the patients. Findings: During 67,095 person-years (mean follow-up 11·7 years, mean age 57·3, 52·5% female), we documented 590 death events. Higher consumption of processed meat was associated with an increased risk of all-cause mortality in patients with IBD (HR comparing >4·0 with 0–0·9 time/week=1·52, 95% confidence interval (CI) 1·05–2·19), but the P-trend for each 25 g increment was 0·075. This association remained significant in patients with Crohn's disease (HR 1·77, 95% CI 1·01–3·10) but not in patients with ulcerative colitis (HR 1·34, 95% CI 0·82–2·20). Consumptions of fish (HR 1·27, 95% CI 0·84–1·91), unprocessed poultry (HR 0·59, 95% CI 0·28–1·21), or unprocessed red meat (HR 0·87, 95% CI 0·60–1·26) were not significantly associated with the mortality of patients with IBD. Interpretation: More frequent consumption of processed meat was associated with an increased risk of mortality in patients with IBD, while no associations were observed for consumption of other types of meat. Our exploratory and speculative findings should be cautiously interpreted and need further replication in other cohorts. Funding: The National Natural Science Foundation of China (81,970,494); Key Project of Research and Development Plan of Hunan Province (2019SK2041).

Abstract Background Percutaneous kyphoplasty (PKP) is a procedure performed by a spine surgeon who undergoes either orthopedic or neurosurgical training. The relationship between short-term adverse outcomes and spine specialty is presently unknown. To compare short-term adverse outcomes of single-level PKP when performed by neurosurgeons and orthopedic surgeons in order to develop more concretely preventive strategies for patients under consideration for single-level PKP. Methods We evaluated patients who underwent single-level PKP from 2012 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). We used univariate analysis and multivariate logistic regression to assess the association between spine surgeon specialty and short-term adverse events, including postoperative complication and unplanned readmission, and to identify different independent risk predictors between two specialties. Results Of 2248 patients who underwent single-level PKP procedure, 1229 patients (54.7%) had their operations completed by a neurosurgeon. There were no significant differences in the development of the majority of postoperative complications and the occurrence of unplanned readmission between the neurosurgical cohort (NC) and the orthopedic cohort (OC). A difference in the postoperative blood transfusion rate (0.7% NS vs. 1.7% OC, P = 0.039) was noted and may due to the differences in comorbidities between patients. Multivariate regression analysis revealed different independent predictors of postoperative adverse events for the two spine specialties. Conclusions By comparing a large range of demographic feature, preoperative comorbidities, and intraoperative factors, we find that short-term adverse events in single-level PKP patients does not affect by spine surgeon specialty, except that the OC had higher postoperative blood transfusion rate. In addition, the different perioperative predictors of postoperative complications and unplanned readmissions were identified between the two specialties. These findings can lead to better evidence-based patient counseling and provide valuable information for medical evaluation and potentially devise methods to reduce patients’ risk.

Background: Whether a gluten-free diet (GFD) is a cause of irritable bowel syndrome (IBS) remains controversial. We aim at exploring the causal relationship between gluten intake and IBS within Mendelian randomization (MR) design.Methods: We conducted a two-sample MR and selected single-nucleotide polymorphisms (SNPs) associated with GFD as instrumental variables (IVs). SNPs and genetic associations with GFD and IBS were obtained from the latest genome-wide association studies (GWAS) in Europeans (GFD: cases: 1,376; controls: 63,573; IBS: cases:1,121; controls: 360,073). We performed inverse variance weighting (IVW) as the primary method with several sensitivity analyses like MR-Egger and MR-PRESSO for quality control. The above analyses were re-run using another large dataset of IBS, as well as changing the p-value threshold when screening IVs, to verify the stability of the results.Results: The final estimate indicated significant causal association [per one copy of effect allele predicted log odds ratio (OR) change in GFD intake: OR = 0.97, 95% confidence interval (CI) 0.96 to 0.99, p < 0.01] without heterogeneity statistically (Q = 2.48, p = 0.78) nor horizontal pleiotropy biasing the causality (p = 0.92). Consistent results were found in validation analyses. Results of MR Steiger directionality test indicated the accuracy of our estimate of the causal direction (Steiger p < 0.001).Conclusion: GFD might be a protective factor of IBS. Therefore, we suggest taking a diet of lower gluten intake into account in IBS prevention and clinical practice.

Objective: This study reviews our experiences in surgical clipping of previously coiled aneurysms, emphasizing on recurrence mechanism of intracranial aneurysms (IAs) and surgical techniques for different types of recurrent IAs.Method: We performed a retrospective study on 12 patients who underwent surgical clipping of aneurysms following endovascular treatment between January 2010 and October 2020. The indications for surgery, surgical techniques, and clinical outcomes were analyzed.Result: Twelve patients with previously coiled IAs were treated with clipping in this study, including nine females and three males. The reasons for the patients having clipping were as follows: early surgery (treatment failure in two patients, postoperative early rebleeding in one patient, and intraprocedural aneurysm rupture during embolization in one patient) and late surgery (aneurysm recurrence in five patients, SAH in one, mass effect in one, and aneurysm regrowth in one). All aneurysms were clipped directly, and coil removal was performed in four patients. One patient died (surgical mortality, 8.3%), 1 patient (8.3%) experienced permanent neurological morbidity, and the remaining 10 patients (83.4%) had good outcomes. Based on our clinical data and previous studies, we classified the recurrence mechanism of IAs into coil compaction, regrowth, coil migration, and coil loosening. Then, we elaborated the specific surgical planning and timing of surgery depending on the recurrence type of IAs.Conclusion: Surgical clipping can be a safe and effective treatment strategy for the management of recurrent coiled IAs, with acceptable morbidity and mortality in properly selected cases. Our classification of recurrent coiled aneurysms into four types helps to assess the optimal surgical approach and the associated risks in managing them.

Purpose: Transsphenoidal surgery is the first-line treatment for Cushing’s disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. Patients and Methods: Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. Results: Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). Conclusions: In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism.

Treatment of drug-resistant forms of cancer requires consideration of their hallmark features, such as abnormal cell death mechanisms or mutations in drug-responding molecular pathways. Malignant cells differ from their normal counterparts in numerous aspects, including copper metabolism. Intracellular copper levels are elevated in various cancer types, and this phenomenon could be employed for the development of novel oncotherapeutic approaches. Copper maintains the cell oxidation levels, regulates the protein activity and metabolism, and is involved in inflammation. Various copper-based compounds, such as nanoparticles or metal-based organic complexes, show specific activity against cancer cells according to preclinical studies. Herein, we summarize the major principles of copper metabolism in cancer cells and its potential in cancer theranostics.

Background: The cardioprotective diet was reported to be associated with several chronic cardiometabolic diseases through an anti-inflammation effect. However, the association between the cardioprotective diet and the risk of inflammatory bowel disease (IBD) was unclear and deserved to be further explored. Methods: We calculated the cardioprotective diet score based on the consumptions of seven common food groups using the validated food frequency questionnaire data in the UK Biobank. Incident IBD was ascertained from primary care data, inpatient data, and the death registry. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the cardioprotective diet score and the risk of IBD. Results: During a mean follow-up of 12.1 years, we documented 2717 incident IBD cases, including 851 cases of Crohn’s disease and 1866 cases of ulcerative colitis. Compared to participants with a cardioprotective diet score of 0–1, we observed a decreased risk of IBD among participants with cardioprotective diet scores of 3 (HR 0.85, 95% CI 0.73–0.99), 4 (HR 0.84, 95% CI 0.72–0.98), and 5–7 (HR 0.77, 95% CI 0.66–0.89) (p-trend < 0.001). Conclusions: A greater adherence to the cardioprotective diet was associated with a lower risk of IBD. Our finding highlighted the importance of focusing on the cardioprotective diet to prevent IBD.

BackgroundObservational studies suggest an association between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn’s disease (CD)] and Primary sclerosing cholangitis (PSC), but the causal association between the two diseases remains unclear.MethodsWe used two-sample Mendelian randomization (MR) to estimate the causal association between IBD and PSC. We chose single nucleotide polymorphisms (SNPs) data for analysis, obtained from previous genome-wide association studies (GWASs). Pleiotropy, heterogeneity, and sensitivity analyses were performed for quality control.ResultsWe found that the causal associations between IBD (both UC and CD) and PSC were significant (e.g., IBD and PSC, Robust adjusted profile score (RAPS) OR = 1.29, 95% CI 1.16∼1.44, p< 0.01; UC and PSC, RAPS OR = 1.40, 95% CI 1.23∼1.58, p< 0.01; CD and PSC, RAPS OR = 1.13, 95% CI 1.02∼1.26, p = 0.02). MR Egger, IVW, and ML tests found statistical heterogeneity between determined IV estimates. The leave-one-out analysis also indicated the sensitivity of the SNPs (e.g., IBD and PSC, MR-Egger Q = 644.30, p< 0.01; UC and PSC, MR-Egger Q = 378.30, p< 0.01; UC and PSC, MR-Egger Q = 538.50, p < 0.01).ConclusionMR analyses support the positive causal effect of IBD (including UC and CD) on PSC in a European population. We provide suggestions for preventing and treating the two diseases.

An ultra-low power always-on keyword spotting (KWS) accelerator is implemented in 22nm CMOS technology, which is based on an optimized convolutional neural network (CNN). To reduce the power consumption while maintaining the system recognition accuracy, we first perform a bit-width quantization method on the proposed CNN to reduce the data/weight bit width required by the hardware computing unit without reducing the recognition accuracy. Then, we propose an approximate computing architecture for the quantized CNN using voltage-domain analog switching network based multiplication and addition unit. Implementation results show that this accelerator can support 10 keywords real time recognition under different noise types and SNRs, while the power consumption can be significantly reduced to 52 μW.

Intracerebral hemorrhage (ICH) is a particularly severe form of stroke, and reactive astrogliosis is a common response following injury to the central nervous system (CNS). Mesenchymal stem cells (MSCs) are reported to promote neurogenesis and alleviate the late side effects in injured brain regions. Gap junctions (Gjs) are abundant in the brain, where the richest connexin (Cx) is Cx43, most prominently expressed in astrocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor regulating antioxidant reactions. Here, we aimed to explore whether bone marrow MSCs (BM-MSCs) could alleviate brain injury and protect astrocytes from apoptosis, by regulating Cx43 and Nrf2. We validated the effect of BM-MSC transplantation in an ICH model in vivo and in vitro and detected changes using immunofluorescence, as well as protein and mRNA expression of glial fibrillary acidic protein (GFAP), vimentin (VIM), Cx43, Nrf2, and heme oxygenase-1 (HO-1). Our results showed that BM-MSC transplantation attenuated brain injury after ICH and upregulated VIM expression in vivo and in vitro. Additionally, Cx43 upregulation and Nrf2 nuclear translocation were observed in astrocytes cocultured with BM-MSC. Knockdown of Cx43 by siRNA restrained Nrf2 nuclear translocation. Cx43 and Nrf2 had a connection as determined by immunofluorescence and coimmunoprecipitation. We demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and have anti-apoptotic abilities after BM-MSC transplantation, where Cx43 upregulation triggers Nrf2 nuclear translocation and promotes its phase II enzyme expression. The Cx43/Nrf2 interaction of astrocytes after BM-MSC transplantation may provide an important therapeutic target in the management of ICH.

Avian leukosis virus subgroup J (ALV-J) is an immunosuppressive virus which has caused heavy losses to the poultry breeding industry. Currently, there is no effective medicine to treat this virus. In our previous experiments, the low-molecular-weight Sargassum fusiforme polysaccharide (SFP) was proven to possess antiviral activity against ALV-J, but its function was limited to the virus adsorption stage. In order to improve the antiviral activity of the SFP, in this study, three new SFP long-chain alkyl group nanomicelles (SFP-C12M, SFP-C14M and SFP-C16M) were prepared. The nanomicelles were characterized according to their physical and chemical properties. The nanomicelles were characterized by particle size, zeta potential, polydispersity index, critical micelle concentration and morphology. The results showed the particle sizes of the three nanomicelles were all approximately 200 nm and SFP-C14M and SFP-C16M were more stable than SFP-C12M. The newly prepared nanomicelles exhibited a better anti-ALV-J activity than the SFP, with SFP-C16M exhibiting the best antiviral effects in both the virus adsorption stage and the replication stage. The results of the giant unilamellar vesicle exposure experiment demonstrated that the new virucidal effect of the nanomicelles might be caused by damage to the phospholipid membrane of ALV-J. This study provides a potential idea for ALV-J prevention and development of other antiviral drugs.

Secondary injuries mediated by oxidative stress lead to deterioration of neurological functions after intracerebral hemorrhage (ICH). Cortical astrocytes are among the most important cells in the central nervous system (CNS), and play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemin is a product of hemoglobin degradation, which has strong toxicity and can induce reactive oxygen species (ROS). Melatonin (Mel) and its metabolites are well tolerated without toxicity, prevent tissue damage as well as effectively assist in scavenging free radicals. We evaluated the hemin neurotoxicity to astrocytes and the resistance of Mel-treated astrocytes to hemin neurotoxicity. And we found Mel induced PKCα phosphorylation (p-PKC), nuclear translocation of Nrf2 in astrocytes, and upregulation of HO-1, which contributed to the reduction of ROS accumulation and cell apoptosis. Nrf2 and HO1 protein expression upregulated by Mel were decreased after administration of PKC inhibitor, Ro 31-8220 (Ro 31). Luzindole (Luz), a melatonin receptor inhibitor, suppressed p-PKCα, HO-1, and Nrf2 expression upregulated by Mel and increased cell apoptosis rate. The upregulation of HO-1 induced by Mel was depressed by knocking down Nrf2 expression by siRNA, which also decreased the resistance of astrocytes to toxicity of hemin. Mel activates astrocytes through PKCα/Nrf2/HO-1 signaling pathway to acquire resistance to toxicity of hemin and resist from oxidative stress and apoptosis. The positive effect of Mel on PKCα/Nrf2/HO-1 signaling pathway may become a new target for neuroprotection after intracerebral hemorrhage.

The edible seaweed Caulerpa lentillifera, a powerful natural food source that is rich in protein, minerals, dietary fibers, vitamins, saturated fatty acids and unsaturated fatty acids, has been mass cultured in some Asian countries and has been the focus of researchers in recent years. Here, the operational conditions of its culture, application in wastewater treatment, and bioactive components are summarized and comparatively analyzed. Based on previous studies, salinity, nutrient concentrations, irradiance and temperature are stress factors for algal growth. Moreover, dried Caulerpa lentillifera seaweed is efficient in the biosorption of heavy metals and cationic dyes in wastewater, and fresh seaweed can be introduced as a biofilter in aquaculture system treatment. In addition, among the rich bioactive compounds in Caulerpa lentillifera, the phenolic compounds show the potential ability for regulating glucose metabolism in vivo. Polysaccharides and oligosaccharides exhibit anticoagulant, immunomodulatory effects and cancer-preventing activity. Siphonaxanthin is a compound with attractive novel functions in cancer-preventing activity and lipogenesis-inhibiting effects. Furthermore, the antioxidant activity of siphonaxanthin extracted from Caulerpa lentillifera could be stronger than that of astaxanthin. This review offers an overview of studies of Caulerpa lentillifera addressing various aspects including cultivation, wastewater treatment and biological active components which may provide valuable information for the cultivation and utilization of this green alga.

The present work characterized and modelled the interfacial heat transfer coefficient and friction coefficient of a non-alloy martensitic steel, for a novel Fast light Alloy Stamping Technology (FAST) process. These models were validated through temperature evolution, thickness distribution and springback measurements on experimentally formed demonstrator components, which were conducted on a pilot production line and showed close agreement, with less than 10% variation from experimental results. The developed models and finite element simulations presented in this work demonstrate that non-isothermal processes can be precisely simulated with implementation of the accurate thermomechanical boundary conditions.

Integer linear programming (ILP) has been widely applied to solve the optimal phasor measurement unit (PMU) placement (OPP) problem for its computational efficiency. Using ILP, a placement with minimum number of Phasor Measurement Units (PMUs) and maximum measurement redundancy can be obtained while ensuring system observability. Author response: please delete this above sentence. However, the existing ILP-based OPP methods does not guarantee full coverage of solutions to the optimization problem, which may sequentially results in suboptimal supervision of the system. In this paper, a hybrid ILP-based method is proposed to cover all solutions to the OPP problem without any omission. Comparing with the existing exhaustive searching methods, the proposed method is more computationally efficient, which makes finding all solutions in a large system a more feasible problem.

In this study, polysaccharides from Grateloupia filicinia (GFP) were extracted and several low molecular weight (Mw) G. filicina polysaccharides (LGFPs) were prepared by the hydrogen peroxide (H2O2) oxidation method. Additionally, the effect of different experimental conditions on the degradation of GFP was determined. Results showed that the GFP degradation rate was positively related to H2O2 concentration and temperature, and negatively related to pH. Chemical analysis and Fourier transform infrared spectra (FT-IR) of GFP and LGFPs showed that the degradation caused a slight decrease of total sugar and sulfate content. However, there was no obvious change for monosaccharide contents. Then, the anti-ALV-J activity of GFP and LGFPs were determined in vitro. Results revealed that all of the samples could significantly inhibit ALV-J and lower Mw LGFPs exhibited a stronger suppression, and that the fraction LGFP-3 with Mw 8.7 kDa had the best effect. In addition, the reaction phase assays showed that the inhibition effect was mainly because of the blocking virus adsorption to host cells. Moreover, real-time PCR, western-blot, and IFA were further applied to evaluate the blocking effects of LGFP-3. Results showed that the gene relative expression and gp85 protein for LGFPS-3 groups were all reduced. Data from IFA showed that there was less virus infected cells for 1000 and 200 μg/mL LGFPS-3 groups when compared to virus control. Therefore, lower Mw polysaccharides from G. filicina might supply a good choice for ALV-J prevention and treatment.

BACKGROUND:A number of studies have reported an association of angiotensin-converting enzyme (ACE) gene polymorphism with primary intracerebral hemorrhage (PICH), however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH. METHODS:PubMed and Embase databases (through Dec 2012) were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs) were estimated and potential sources of heterogeneity and bias were explored. RESULTS:A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07-2.35 for DD vs. DI+II). However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16-2.66 for DD vs. DI+II), but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36-3.88, P = 0.784 for DD vs. DI+II). The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models. CONCLUSIONS:These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.

Precise in vivo evaluation of cerebral vasospasm caused by subarachnoid hemorrhage has remained a critical but unsolved issue in experimental small animal models. In this study, we used synchrotron radiation angiography to study the vasospasm of anterior circulation arteries in two subarachnoid hemorrhage models in rats. Synchrotron radiation angiography, laser Doppler flowmetry-cerebral blood flow measurement, [(125)I]N-isopropyl-p-iodoamphetamine cerebral blood flow measurement and terminal examinations were applied to evaluate the changes of anterior circulation arteries in two subarachnoid hemorrhage models made by blood injection into cisterna magna and prechiasmatic cistern. Using synchrotron radiation angiography technique, we detected cerebral vasospasm in subarachnoid hemorrhage rats compared to the controls (p