Comprehensive comparison of integrated fixed-film activated sludge (IFAS) and AAO activated sludge methods: Influence of different operational parameters.

Due to limited land availability in municipal wastewater treatment plants, integrated fixed-film activated sludge (IFAS) technology offers significant advantages in improving nitrogen removal performance and treatment capacity. In this study, two systems, IFAS and Anaerobic-Anoxic-Oxic Activated sludge process (AAO), were compared by adjusting parameters such as hydraulic retention time (HRT), nitrifying solution recycle ratio, sludge recycle ratio, and dissolved oxygen (DO). The objective was to investigate pollutant removal capacity and differences in microbial community composition between the two systems. The study showed that, at an HRT of 12 h, the IFAS system exhibited an average increase of 5.76%, 8.85%, and 12.79% in COD, NH4+-N, and TN removal efficiency respectively, compared to the AAO system at an HRT of 16 h. The TP concentration in the IFAS system reached 0.82 mg/L without the use of additives. The IFAS system demonstrated superior effluent results under lower operating conditions of HRT, nitrification solution recycle ratio, and DO. The 16S rDNA analysis revealed higher abundance of denitrification-related associated flora, including Proteobacteria, Bacteroidetes, and Planctomycetota, in the IFAS system compared to the AAO system. Similarities were observed between microorganisms attached to the media and activated sludge in the anaerobic, anoxic, and oxic tanks. q-PCR analysis indicated that the incorporation of filler material in the IFAS system resulted in similar abundance of nitrifying bacteria genes on the biofilm as in the oxic tank. Additionally, denitrifying genes showed higher levels due to aeration scouring and the presence of alternating aerobic-anaerobic environments on the biofilm surface, enhancing nitrogen removal efficiency.

Supermolecular Confined Silicon Phosphorescence Nanoprobes for Time-Resolved Hypoxic Imaging Analysis.

Room temperature phosphorescence (RTP) nanoprobes play crucial roles in hypoxia imaging due to their high signal-to-background ratio (SBR) in the time domain. However, synthesizing RTP probes in aqueous media with a small size and high quantum yield remains challenging for intracellular hypoxic imaging up to present. Herein, aqueous RTP nanoprobes consisting of naphthalene anhydride derivatives, cucurbit[7]uril (CB[7]), and organosilicon are reported via supermolecular confined methods. Benefiting from the noncovalent confinement of CB[7] and hydrolysis reactions of organosilicon, such small-sized RTP nanoprobes (5-10 nm) exhibit inherent tunable phosphorescence (from 400 to 680 nm) with microsecond second lifetimes (up to ∼158.7 µs) and high quantum yield (up to ∼30%). The as-prepared RTP nanoprobes illustrate excellent intracellular hypoxia responsibility in a broad range from ∼0.1 to 21% oxygen concentrations. Compared to traditional fluorescence mode, the SBR value (∼108.69) of microsecond-range time-resolved in vitro imaging is up to 2.26 times greater in severe hypoxia (<0.1% O2), offering opportunities for precision imaging analysis in a hypoxic environment.

Atomic structures of a bacteriocin targeting Gram-positive bacteria.

Due to envelope differences between Gram-positive and Gram-negative bacteria1, engineering precision bactericidal contractile nanomachines2 requires atomic-level understanding of their structures; however, only those killing a Gram-negative bacterium are currently known3,4. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar protein linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with differences between their targeted envelopes. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire length of the diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.

Evaluation of water ecological health of Yanhe River based on benthic fauna integrity index.

Yanhe River Basin is located in the hilly gully area of the Loess Plateau with serious soil erosion. Strong human activities in the middle and lower reaches lead to fragile ecological environment. Soil erosion status varies among different geomorphic units within the watershed (loess liang hilly and gully region, loess mao hilly and gully region, and broken platform region). In this study, we surveyed the benthic community from the Yanhe River Basin in April (spring) and October (autumn) of 2021. To evaluate the water ecological health status of the watershed and investigate the effects of different geomorphic units on the benthic integrity of the benthos, we constructed the benthic-index of biotical integrity (B-IBI) based on the biological data. We identified a total of 113 species of 73 genera in 4 phyla of benthic fauna, with aquatic insects as the dominant taxa in both seasons. Through screening 26 candidate indicators, we found that the spring B-IBI consisted of three indicators: relative abundance of individuals of dominant taxonomic units, family biotic index (FBI), and relative abundance of predator individuals, and that autumn B-IBI was composed of the number of taxonomic units of Ephemeroptera, FBI value, and the relative abundance of predator individuals. Results of the B-IBI evaluation showed that 83.3% of the sampling sites in the upper mainstem and tributaries were at a healthy condition, while only 28.6% sampling sites in the middle and lower mainstem and tributaries were at a healthy condition. In addition, the health status of the watershed was better in spring than in autumn. The Kruskal-Wallis nonparametric tests showed that benthic density, species number, and B-IBI percentile scores in the fragmented loess area were significantly higher in spring than in autumn, and significantly lower in autumn than in the loess liang hilly and gully region and loess mao hilly and gully region, being mainly caused by the increasing erosion due to the concentrated rainfall in wet season. Results of the redundancy analysis showed that key environmental factors affecting benthic community structure in spring were boulder substrate, chlorophyll-a, oxidation reduction potential, turbidity, conductivity, and dissolved oxygen, and were nitrate-nitrogen, oxidation reduction potential, and pH in autumn.

Optimization and preparation of a compound cod liver oil film former agent: an orthogonal design.

Background: Cod liver oil has anti-inflammatory properties and could help regulate recurrent aphthous stomatitis (RAS). An orthogonal experiment was used to evaluate and improve the dosage form of compound cod liver oil, which has replaced the previously used liniment preparation based on film method. Methods: An orthogonal experiment was adopted, and the appearance and film-forming time of the film coating agents were used as indicators. The optimal ratio in the preparation process for the compound cod liver oil film agent was then optimized. A method for determination of compound cod liver oil film was established using High-Performance Liquid Chromatography (HPLC). Results: The results indicate that the blank films prepared using 55 mg polyvinyl alcohol (PVA) (PVA low), 45 mg of PVA (PVA medium), and 10 mg glycerol had the optimal performance, which was defined as PVAa. The drug-carrying film prepared from 3 mL PVAa (i.e., film-forming material with the optimal proportion), 30 mg dexamethasone acetate, and 30 mg metronidazole had the optimal performance. The verified sample has a complete and smooth appearance, uniform thickness and color, and no evident bubbles, which meets the requirements for a film agent defined in the Chinese Pharmacopoeia, 2020 edition. HPLC was used to determine the major components: dexamethasone acetate, metronidazole, and dyclonine hydrochloride, and the optimal separation effect was obtained. The method has advantages of good specificity, good linear results, high recovery rate, and good repeatability. Conclusion: This study proposes an optimized compound cod liver oil film former agent and preparation method. The results indicate that the compound cod liver oil film former agent had good performance, reflecting the high feasibility of this research method. The detection method of compound cod liver oil film was established by HPLC. The method was feasible, and the validity and stability of the formulation and preparation technology were guaranteed. The role of the newly developed agent in patients with RAS should be investigated further.

Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

Multi-colour room-temperature phosphorescence from fused-ring compounds for dynamic anti-counterfeiting applications.

We present a facile strategy to achieve purely organic multi-colour room-temperature phosphorescence (RTP) films by doping typical fused-ring compounds into a poly(vinyl alcohol) matrix. Such RTP films demonstrate inherent RTP emission ranging from green to red with a long lifetime and high quantum yield (QY) (lifetime: ∼0.56 ms, QY: ∼35.4%). We further exploit such high-performance RTP films for dynamic information encryption.

Framework Nucleic Acids Combined with 3D Hybridization Chain Reaction Amplifiers for Monitoring Multiple Human Tear Cytokines.

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.1 pg mL-1, consuming as little as 3 mL of tear fluid. Double-blind testing of clinical DES samples using the developed sensor and commercial ELISA shows no significant difference between them. Compared with single-biomarker diagnosis, the diagnostic accuracy of this sensor based on multiple biomarkers has improved by ≈16%. The developed system offers the potential for tear sensors to enable personalized and accurate diagnosis of various ocular diseases.

Laboratory Data Timeliness and Completeness Improves Following Implementation of an Electronic Laboratory Information System in Côte d'Ivoire: Quasi-Experimental Study on 21 Clinical Laboratories From 2014 to 2020.

BACKGROUND: The Ministry of Health in Côte d'Ivoire and the International Training and Education Center for Health at the University of Washington, funded by the United States President's Emergency Plan for AIDS Relief, have been collaborating to develop and implement the Open-Source Enterprise-Level Laboratory Information System (OpenELIS). The system is designed to improve HIV-related laboratory data management and strengthen quality management and capacity at clinical laboratories across the nation. OBJECTIVE: This evaluation aimed to quantify the effects of implementing OpenELIS on data quality for laboratory tests related to HIV care and treatment. METHODS: This evaluation used a quasi-experimental design to perform an interrupted time-series analysis to estimate the changes in the level and slope of 3 data quality indicators (timeliness, completeness, and validity) after OpenELIS implementation. We collected paper and electronic records on clusters of differentiation 4 (CD4) testing for 48 weeks before OpenELIS adoption until 72 weeks after. Data collection took place at 21 laboratories in 13 health regions that started using OpenELIS between 2014 and 2020. We analyzed the data at the laboratory level. We estimated odds ratios (ORs) by comparing the observed outcomes with modeled counterfactual ones when the laboratories did not adopt OpenELIS. RESULTS: There was an immediate 5-fold increase in timeliness (OR 5.27, 95% CI 4.33-6.41; P<.001) and an immediate 3.6-fold increase in completeness (OR 3.59, 95% CI 2.40-5.37; P<.001). These immediate improvements were observed starting after OpenELIS installation and then maintained until 72 weeks after OpenELIS adoption. The weekly improvement in the postimplementation trend of completeness was significant (OR 1.03, 95% CI 1.02-1.05; P<.001). The improvement in validity was not statistically significant (OR 1.34, 95% CI 0.69-2.60; P=.38), but validity did not fall below pre-OpenELIS levels. CONCLUSIONS: These results demonstrate the value of electronic laboratory information systems in improving laboratory data quality and supporting evidence-based decision-making in health care. These findings highlight the importance of OpenELIS in Côte d'Ivoire and the potential for adoption in other low- and middle-income countries with similar health systems.

Triboelectric-Responsive Drug Delivery Hydrogel for Accelerating Infected Wound Healing.

Electrotherapy is of great interest in the field of tissue repair as an effective, well-tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F-TENG) and a triboelectric-responsive drug delivery hydrogel (TR-DDH) for healing of bacterium-infected wounds. F-TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR-DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart-responsive drug delivery systems.

The causal relationship between depression and obstructive sleep apnea: A bidirectional Mendelian randomization study.

OBJECTIVE: Numerous studies have reported the close association of depression with obstructive sleep apnea (OSA). However, the causal nature and direction remain unclear. This study aimed to identify the genetic causal relationship between depression and OSA using Mendelian randomization (MR). METHODS: Based on publicly available genome-wide association studies data of depression and OSA, we conducted a bidirectional two-sample MR study. The inverse-variance weighted (IVW) was used as the main analysis method. Moreover, multivariable MR was performed to further explore the underlying genetic causality of OSA and depression after adjusting for several potential mediators. RESULTS: The univariable MR analysis revealed a significant causality of depression on the susceptibility of OSA (ORivw = 1.29, 95%CI:1.11,1.50; p < 0.001). This relationship was evidenced by the phenotypes for broad depression (ORivw = 3.30, 95%CI: 1.73, 6.29; p < 0.001), probable major depression (ORivw = 18.79, 95%CI: 5.69, 61.99; p < 0.001), and ICD-10 major depression (ORivw = 23.67, 95%CI: 4.13, 135.74; p < 0.001). In the reverse direction, no significant causal effect of OSA on depression was found. After adjusting for smoking, alcohol use, obesity, type 2 diabetes, insomnia, age, gender, and codeine, most of these results suggested that depression remained significantly and positively associated with OSA. CONCLUSION: These findings may contribute to the understanding of the etiology of depression and OSA and also suggest the clinical significance of controlling depression for the prevention of OSA.

Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.

RNA splicing shapes the gene regulatory programs that underlie various physiological and disease processes. Here, we present the SCASL (single-cell clustering based on alternative splicing landscapes) method for interrogating the heterogeneity of RNA splicing with single-cell RNA-seq data. SCASL resolves the issue of biased and sparse data coverage on single-cell RNA splicing and provides a new scheme for classifications of cell identities. With previously published datasets as examples, SCASL identifies new cell clusters indicating potentially precancerous and early-tumor stages in triple-negative breast cancer, illustrates cell lineages of embryonic liver development, and provides fine clusters of highly heterogeneous tumor-associated CD4 and CD8 T cells with functional and physiological relevance. Most of these findings are not readily available via conventional cell clustering based on single-cell gene expression data. Our study shows the potential of SCASL in revealing the intrinsic RNA splicing heterogeneity and generating biological insights into the dynamic and functional cell landscapes in complex tissues.

Domain-Targeted Membrane Partitioning of Specific Proteins with DNA Nanodevices.

The cell membrane exhibits a remarkable complexity of lipids and proteins that dynamically segregate into distinct domains to coordinate various cellular functions. The ability to manipulate the partitioning of specific membrane proteins without involving genetic modification is essential for decoding various cellular processes but highly challenging. In this work, by conjugating cholesterols or tocopherols at the three bottom vertices of the DNA tetrahedron, we develop two sets of nanodevices for the selective targeting of lipid-order (Lo) and lipid-disorder (Ld) domains on the live cell membrane. By incorporation of protein-recognition ligands, such as aptamers or antibodies, through toehold-mediated strand displacement, these DNA nanodevices enable dynamic translocation of target proteins between these two domains. We first used PTK7 as a protein model and demonstrated, for the first time, that the accumulation of PTK7 to the Lo domains could promote tumor cell migration, while sequestering it in the Ld domains would inhibit the movement of the cells. Next, based on their modular nature, these DNA nanodevices were extended to regulate the process of T cell activation through manipulating the translocation of CD45 between the Lo and the Ld domains. Thus, our work is expected to provide deep insight into the study of membrane structure and molecular interactions within diverse cell signaling processes.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons.

Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA.

Androgen-repressed lncRNA LINC01126 drives castration-resistant prostate cancer by regulating the switch between O-GlcNAcylation and phosphorylation of androgen receptor.

BACKGROUND: Prostate cancer (PCa) initially shows satisfactory response to therapies targeting the androgen receptor (AR). However, progression to a castration-resistant stage indicates poor prognosis in PCa patients. AR signalling still plays a central role in most castration-resistant prostate cancers (CRPC). Therefore, unveiling the mechanisms of AR reactivation under androgen-deprived conditions is imperative to discover novel therapeutic targets for CRPC. METHODS: Using an integrative analysis of the transcriptomics of three independent PCa cohorts and a published landscape of AR-regulated long non-coding RNA (lncRNA), lncRNA LINC01126 was selected as a candidate gene that could drive CRPC progression for further study. Quantitative reverse transcription polymerase chain reaction, in situ hybridisation (ISH) and fluorescent ISH were performed to detect LINC01126 in PCa tissues and cells. The functional role and mechanism of LINC01126 were further investigated using in vitro and in vivo gain and loss of function assays. RESULTS: LINC01126, identified as an AR-repressed lncRNA, was significantly upregulated after AR-targeted therapies. In addition, we found that LINC01126 was upregulated in CRPC and was associated with poor prognosis. We also proved that LINC01126 stabilised AR protein and enhanced AR nuclear translocation and transactivation by promoting the transition from O-GlcNAcylation at threonine 80 to phosphorylation at serine 81 (S81) within the AR protein. Mechanism analysis revealed that LINC01126 facilitates the interaction of CDK9 with AR and impedes the binding of O-linked N-acetylglucosamine (O-GlcNAc) transferase to AR. Consequently, LINC01126 expression was sufficient to activate AR signalling without androgen. LINC01126 overexpression increased, whereas LINC01126 knockdown decreased castration resistance traits in PCa cells in vitro and in vivo. Furthermore, our data showed that LINC01126-targeting antisense oligonucleotides (ASO) substantially inhibited CRPC cells in vitro. CONCLUSIONS: Our research expands the functions of AR-regulated lncRNA in sustaining androgen-independent AR activity and promoting CRPC progression and reveals that LINC01126 may be a new therapeutic target for PCa.

Predicting Factors of Long-term Outcome of Gastrointestinal Behçet's Disease: A Chinese Retrospective Study.

PURPOSE: Behçet's disease (BD) is a complex disorder affecting multiple systems and organs, and gastrointestinal BD is poorly understood. We aimed to identify factors influencing the long-term outcomes of patients with gastrointestinal BD. METHODS: Consecutive patients with gastrointestinal BD were analyzed retrospectively. Data on the following clinical characteristics were collected: sex, age at diagnosis, symptoms, endoscopic findings, medical treatments, and surgery. Mucosal healing and surgical rates at 1, 2, and 5 years were evaluated. Log-rank test and Cox proportional hazards regression models were used to evaluate the factors affecting long-term outcomes. FINDINGS: Baseline data of 175 patients with gastrointestinal BD were included. The mean (SD) age at diagnosis was 38.3 (12.9) years. The typical clinical symptoms were oral ulcer (72.6%), abdominal pain (71.4%), and weight loss (41.1%). The most commonly involved location was the ileocecum; isolated oval ulcer was the most common ulcer type. Seventeen patients (9.7%) underwent 18 surgeries after inclusion. The cumulative surgical rates were 8.6% (n/N = 15/175), 8.6% (n/N = 15/175), and 9.1% (n/N = 16/175) in 1, 2, and 5 years, respectively. Data from 101 patients who underwent at least 2 endoscopies were included in the analysis for mucosal healing. Kaplan-Meier curve showed that the cumulative mucosal healing rates at 1, 2, and 5 years were 34.7% (n/N = 35/101), 41.6% (n/N = 42/101), and 61.4% (n/N = 62/101), respectively. We compared cumulative mucosal healing rates between 4 treatment groups, including 5-aminosalicylic acid (3% [n/N = 3/101]), mono-immunosuppressant (31.7% [n/N = 32/101]), combined therapy (36.6% [n/N = 37/101]), and escalation therapy (28.7% [n/N = 29/101]), and found that mono-immunosuppressant achieved earlier mucosal healing than combined therapy (P = 0.0008) and escalation therapy (P = 0.0008). The univariate analysis showed that moderate to severe disease activity (P = 0.013, P = 0.004), diameter of the maximal ulcer >4 cm (P = 0.002), and nonsimple esophageal involvement (P < 0.001) were risk factors, and number of ulcers between 2 and 5 was the protective factor of mucosal healing (P = 0.001). Multivariate regression analysis indicated that nonsimple esophageal involvement (P < 0.001) and the maximal ulcer >4 cm (P = 0.041) were independent risk factors of mucosal healing. IMPLICATIONS: Most patients with gastrointestinal BD need long-term treatment to achieve mucosal healing. The location and size of ulcers have a significant impact on the mucosal healing of gastrointestinal BD.

Cardiometabolic diseases and early cognitive decline: Mitigated by integrated active lifestyle for brain health.

BACKGROUND: Cardiometabolic diseases (CMDs) increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. METHODS: This prospective study used the baseline and 2-year follow-up data of 2537 dementia-free elderly ≥60 from PINDEC Project. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking, and alcohol consumption) were collected and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, ≤3 score; intermediate, 4 score; and active, ≥5). Logistic regression was used in data analysis. RESULTS: 35.2 % participants had 5-6 healthy components, while only 5.4 % had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95 % confidence interval) of early cognitive decline was 1.223 (0.799-1.871) and 1.832 (1.140-2.943) for participants with only one CMD and any two or more CMDs, respectively. An inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend = 0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95%CI: 0.302-2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR = 3.422, 95%CI: 1.764-6.638). LIMITATIONS: Our research lacks information about nutrition. CONCLUSIONS: A dose-response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).