A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

Exploring seasonal variations, assembly dynamics, and relationships of bacterial communities in different habitats of marine ranching.

Offshore coastal marine ranching ecosystems provide habitat for diverse and active bacterial communities. In this study, 16S rRNA gene sequencing and multiple bioinformatics methods were applied to investigate assembly dynamics and relationships in different habitats. The higher number of edges in the water network, more balanced ratio of positive and negative links, and more keystone species included in the co-occurrence network of water. Stochastic processes dominated in shaping gut and sediment community assembly (R2 < 0.5), while water bacterial community assembly were dominated by deterministic processes (R2 > 0.5). Dissimilarity-overlap curve model indicated that the communities in different habitats have general dynamics and interspecific interaction (P < 0.001). Bacterial source-tracking analysis revealed that the gut was more similar to the sediment than the water bacterial communities. In summary, this study provides basic data for the ecological study of marine ranching through the study of bacterial community dynamics.

A deep-learning-based threshold-free method for automated analysis of rodent behavior in the forced swim test and tail suspension test.

BACKGROUND: The forced swim test (FST) and tail suspension test (TST) are widely used to assess depressive-like behaviors in animals. Immobility time is used as an important parameter in both FST and TST. Traditional methods for analyzing FST and TST rely on manually setting the threshold for immobility, which is time-consuming and subjective. NEW METHOD: We proposed a threshold-free method for automated analysis of mice in these tests using a Dual-Stream Activity Analysis Network (DSAAN). Specifically, this network extracted spatial information of mice using a limited number of video frames and combined it with temporal information extracted from differential feature maps to determine the mouse's state. To do so, we developed the Mouse FSTST dataset, which consisted of annotated video recordings of FST and TST. RESULTS: By using DSAAN methods, we identify immobility states at accuracies of 92.51 % and 88.70 % for the TST and FST, respectively. The predicted immobility time from DSAAN is nicely correlated with a manual score, which indicates the reliability of the proposed method. Importantly, the DSAAN achieved over 80 % accuracy for both FST and TST by utilizing only 94 annotated images, suggesting that even a very limited training dataset can yield good performance in our model. COMPARISON WITH EXISTING METHOD(S): Compared with DBscorer and EthoVision XT, our method exhibits the highest Pearson correlation coefficient with manual annotation results on the Mouse FSTST dataset. CONCLUSIONS: We established a powerful tool for analyzing depressive-like behavior independent of threshold, which is capable of freeing users from time-consuming manual analysis.

Comparative outcomes of AI-assisted ChatGPT and face-to-face consultations in infertility patients: a cross-sectional study.

BACKGROUND: With the advent of artificial intelligence (AI) in healthcare, digital platforms like ChatGPT offer innovative alternatives to traditional medical consultations. This study seeks to understand the comparative outcomes of AI-assisted ChatGPT consultations and conventional face-to-face interactions among infertility patients. METHODS: A cross-sectional study was conducted involving 120 infertility patients, split evenly between those consulting via ChatGPT and traditional face-to-face methods. The primary outcomes assessed were patient satisfaction, understanding, and consultation duration. Secondary outcomes included demographic information, clinical history, and subsequent actions post-consultation. RESULTS: While both consultation methods had a median age of 34 years, patients using ChatGPT reported significantly higher satisfaction levels (median 4 out of 5) compared to face-to-face consultations (median 3 out of 5; p < 0.001). The ChatGPT group also experienced shorter consultation durations, with a median difference of 12.5 minutes (p < 0.001). However, understanding, demographic distributions, and subsequent actions post-consultation were comparable between the two groups. CONCLUSIONS: AI-assisted ChatGPT consultations offer a promising alternative to traditional face-to-face consultations in assisted reproductive medicine. While patient satisfaction was higher and consultation durations were shorter with ChatGPT, further studies are required to understand the long-term implications and clinical outcomes associated with AI-driven medical consultations. Key Messages What is already known on this topic:  Artificial intelligence (AI) applications, such as ChatGPT, have shown potential in various healthcare settings, including primary care and mental health support. Infertility is a significant global health issue that requires extensive consultations, often facing challenges such as long waiting times and varied patient satisfaction. Previous studies suggest that AI can offer personalized care and immediate feedback, but its efficacy compared with traditional consultations in reproductive medicine was not well-studied. What this study adds:  This study demonstrates that AI-assisted ChatGPT consultations result in significantly higher patient satisfaction and shorter consultation durations compared with traditional face-to-face consultations among infertility patients. Both consultation methods were comparable in terms of patient understanding, demographic distributions, and subsequent actions postconsultation. How this study might affect research, practice, or policy:  The findings suggest that AI-driven consultations could serve as an effective and efficient alternative to traditional methods, potentially reducing consultation times and improving patient satisfaction in reproductive medicine. Further research could explore the long-term impacts and broader applications of AI in clinical settings, influencing future healthcare practices and policies toward integrating AI technologies.

Berberine as a novel ACSL4 inhibitor to suppress endothelial ferroptosis and atherosclerosis.

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process of cell injury through ferroptosis, has the potential to ameliorate cell damage. In this study, we aimed to investigate the potential of berberine (BBR) as an inhibitor of ACSL4 in order to suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created in ApoE-/- mice by feeding a high fat diet for 16 weeks. Additionally, a mouse model with endothelium-specific overexpression of ACSL4 was established. BBR was administered orally to assess its potential therapeutic effects on atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low density lipoprotein (ox-LDL) to simulate atherosclerotic endothelial damage in vitro. The interaction between ACSL4 and BBR has been confirmed, with BBR playing a role in inhibiting erastin-induced ferroptosis by regulating ACSL4. Additionally, BBR has been found to inhibit lipid deposition, plaque formation, and collagen deposition in the aorta, thereby delaying the progression of atherosclerosis. It also restored the abnormal expression of ferroptosis-related proteins in atherosclerotic vascular endothelial cells both in vivo and in vitro. In conclusion, BBR, acting as an ACSL4 inhibitor, can improve atherosclerosis by inhibiting ferroptosis in endothelial cells. This highlights the potential of targeted inhibition of vascular endothelial ACSL4 as a strategy for treating atherosclerosis, with BBR being a candidate for this purpose.

Phenotypic and mutational spectrum of 17 Chinese patients with Menkes Disease.

BACKGROUND: Menkes Disease (MD) is a fatal X-linked recessive disorder caused by mutations in the ATP7A gene. Severe cases typically die before the age of three. Mild MD and occipital horn syndrome are variants of MD characterized by a less severe phenotype and longer survival. OBJECTIVE: This case series aims to validate previous findings, expand the clinical phenotype, identify novel ATP7A mutations of MD patients. METHODS: Observational data with follow-up were collected from 17 genetically diagnosed Chinese MD patients. RESULTS: All 17 patients exhibited neurological symptoms, including delayed motor milestones (100%) and seizures (58.8%). Unspecific pregnancy or delivery complications occurred in 9 patients (52.9%). The most prevalent connective tissue problems were abnormal hair (76.5%), followed by skeletal and dental abnormalities (52.9%), skin problems (41.2%) and hernia (35.3%). Sensorineural hearing loss (17.6%) was previously unreported. Coronary artery aneurysm and patent foramen ovale (5.9%) were infrequent. One 16-year-old boy carries pathological exon 3-4 deletion, presents novel mild phenotype including short stature and cerebellar ataxia. Out of 13 patients with follow-up (median: 24 months), 7 patients (53.8%) died with median survival of 40 months (range: 21-48 months), 3 patients (23.1%) show severe motor development delay and 2 (15.4%) have refractory epilepsy, only the mild MD patient shows improved cerebellar ataxia. Sixteen ATP7A mutations were identified including 6 small indels (37.5%), 5 nonsense mutations (31.2%), 2 missense mutations (12.5%), 2 exon deletions (12.5%), and 1 splice site mutation (6.25%). Fourteen mutations were novel. CONCLUSIONS: Our study further broadens the phenotypic and genotypic spectrums of Menkes disease.

Cell Wall Binding Strategies Based on Cu3SbS3 Nanoparticles for Selective Bacterial Elimination and Promotion of Infected Wound Healing.

Utilizing nanomaterials as an alternative to antibiotics, with a focus on maintaining high biosafety, has emerged as a promising strategy to combat antibiotic resistance. Nevertheless, the challenge lies in the indiscriminate attack of nanomaterials on both bacterial and mammalian cells, which limits their practicality. Herein, Cu3SbS3 nanoparticles (NPs) capable of generating reactive oxygen species (ROS) are discovered to selectively adsorb and eliminate bacteria without causing obvious harm to mammalian cells, thanks to the interaction between O of N-acetylmuramic acid in bacterial cell walls and Cu of the NPs. Coupled with the short diffusion distance of ROS in the surrounding medium, a selective antibacterial effect is achieved. Additionally, the antibacterial mechanism is then identified: Cu3SbS3 NPs catalyze the generation of O2•-, which has subsequently been conversed by superoxide dismutase to H2O2. The latter is secondary catalyzed by the NPs to form •OH and 1O2, initiating an in situ attack on bacteria. This process depletes bacterial glutathione in conjunction with the disruption of the antioxidant defense system of bacteria. Notably, Cu3SbS3 NPs are demonstrated to efficiently impede biofilm formation; thus, a healing of MRSA-infected wounds was promoted. The bacterial cell wall-binding nanoantibacterial agents can be widely expanded through diversified design.

Dyslipidemia characterized by low density lipoprotein cholesterol and risk of preterm Birth: A Mendelian randomization study.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality worldwide, and dyslipidemia is associated with preterm birth in observational studies. We use Mendelian randomization (MR) analyses to uncover the causal association between blood lipid levels and preterm birth. METHODS: We extracted uncorrelated (R2 < 0.001) single-nucleotide polymorphisms strongly associated (p < 5 × 10-8) with blood lipids from genome wide association studies of FinnGen database and UK Biobank participants. Inverse variance weighted method was the main MR analysis. Sensitivity analyses including genetic pleiotropy, heterogeneity, and directionality of causality were conducted. RESULTS: The study included 115,082 participants with lipid measurements, 8,507 patients with preterm birth. Increasing apolipoprotein B (odds ratio (OR), 1.12[95 % CI, 1.02-1.23]; p = 0.019), low-density lipoprotein cholesterol (OR, 1.11[95 % CI, 1.00-1.22]; p = 0.040), non-high-density lipoprotein cholesterol (OR, 1.12[95 % CI, 1.01-1.24]; p = 0.026), remnant cholesterol (OR, 1.11[95 % CI, 1.00-1.23]; p = 0.047) and total free cholesterol (OR, 1.11[95 % CI, 1.01-1.23]; p = 0.037) were associated with increased risk of preterm delivery. Moreover, triglycerides in low-density lipoprotein were causally associated with the risk of PTB. Our sensitivity analysis yielded robust results, uncovering no evidence of horizontal pleiotropy or reverse causal relationships. CONCLUSION: Our investigation unveils the adverse impact of dyslipidemia on preterm birth, with a particular emphasis on the detrimental effect of elevated low-density lipoprotein cholesterol.

Exploring usage pattern variation of free-floating bike-sharing from a night travel perspective.

Free-floating bike sharing (FFBS) attracts increasing research focusing on usage patterns, determining factors, and integrated transportation. However, existing researchers tend to overlook the variation in usage characteristics over various time ranges, particularly the usage pattern at night. This paper is conducted to fill the gap through a series of analysis approaches on FFSB in Beijing. The characteristics of the usage pattern, including time-varying usage and traveling distance distributions, are initially illustrated. Subsequently, the spatial patterns of FFBS are visualized and thoroughly analyzed in different time ranges and origin-destination (O-D) flows. A statistical model evaluating the environmental effects of FFBS trips revealed the source of FFBS usage. In addition to focusing on the nighttime, the usage patterns varying day and night are compared through the analysis. The findings explain the usage pattern variation and the unique pattern at night, providing valuable insight for improving the management of the FFBS system.

Dietary patterns and hepatocellular carcinoma risk: a systematic review and meta-analysis of cohort and case-control studies.

BACKGROUND: Globally, HCC presents a significant health burden, characterized by high incidence and mortality rates. Epidemiological studies have increasingly suggested a link between dietary patterns and the risk of hepatocellular carcinoma (HCC), yet consensus on this relationship remains elusive. OBJECTIVE: This study aims to synthesize existing literature and provide a comprehensive analysis of the association between dietary patterns and HCC risk through meta-analytical methods. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library databases was conducted to identify studies examining common dietary patterns in relation to HCC, published up to August 2023. Study quality was rigorously evaluated using the Newcastle-Ottawa Scale. We employed a random effects model to synthesize effect sizes, calculating hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 13 papers, of these 10 investigating a priori dietary patterns(index-based dietary patterns) and 3 focusing on a posterior dietary patterns (data-driven dietary patterns). Analysis of a priori dietary patterns revealed that higher scores in the Healthy Eating Index (HEI) & alternative HEI (HR = 0.67, 95% CI: 0.54-0.85), Dietary Approaches to Stop Hypertension (DASH) (HR = 0.77, 95% CI: 0.66-0.91), and the Mediterranean diet (HR = 0.65, 95% CI: 0.56-0.75) were associated with a reduced risk of HCC. Conversely, pro-inflammatory dietary patterns were linked with an increased risk (HR = 2.21, 95% CI: 1.58-3.09). In a posterior dietary patterns, a vegetable-based diet was negatively correlated with HCC risk (HR = 0.63, 95% CI: 0.49-0.81). CONCLUSION: This meta-analysis underscores a significant association between dietary patterns and the risk of HCC. Adherence to healthy dietary patterns characterized by high in vegetables, whole grains, legumes, nuts, and low in red and processed meats may confer a protective effect against HCC, whereas inflammatory diets appear to elevate risk.

Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors.

Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing. In the first stage, SUC-MN synergistically enhanced the effect of IL-4 through more potent reprogramming of pro-regenerative M2-like macrophages via the JAK-STAT pathway to increase endogenous GF production. In the second stage, sucralfate binds to GFs and sterically disfavors protease degradation to increase bioavailability of GFs. The IL-4/SUC-MN technology accelerated wound healing by 56.6 % and 46.5 % in diabetic mice wounds and porcine wounds compared to their respective untreated controls. Overall, our findings highlight the innovative use of molecular simulations to identify bioactive ingredients and their incorporation into microneedles for promoting wound healing through multiple synergistic mechanisms.

[Clinical phenotype and genetic analysis of a child with Intellectual developmental disorder and epilepsy due to variant of CLTC gene].

OBJECTIVE: To explore the clinical features and genetic basis for a child with Intellectual developmental disorder (IDD) and epilepsy. METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c.3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3). CONCLUSION: The c.3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.

High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases.

BACKGROUND: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis. METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. CONCLUSION: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Erratum: Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation.

[This corrects the article DOI: 10.1016/j.isci.2024.109122.].

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

Withaferin A protects against epilepsy by promoting LCN2-mediated astrocyte polarization to stopping neuronal ferroptosis.

BACKGROUND: Epilepsy is among the most frequent severe brain diseases, with few treatment options available. Neuronal ferroptosis is an important pathogenic mechanism in epilepsy. As a result, addressing ferroptosis appears to be a promising treatment approach for epilepsy. Withaferin A (WFA) is a C28 steroidal lactone that has a broad range of neuroprotective properties. Nonetheless, the antiepileptic action of WFA and the intrinsic mechanism by which it inhibits ferroptosis following epilepsy remain unknown. PURPOSE: This study aimed at investigating to the antiepileptic potential of WFA in epilepsy, as well as to propose a potential therapeutic approach for epilepsy therapy. METHODS: We conducted extensive research to examine the impacts of WFA on epilepsy and ferroptosis, using the kainic acid (KA)-treated primary astrocyte as an in vitro model and KA-induced temporal lobe epilepsy mice as an in vivo model. To analyze the neuroprotective effects of WFA on epileptic mice, electroencephalogram (EEG) recording, Nissl staining, and neurological function assessments such as the Morris water maze (MWM) test, Y-maze test, Elevated-plus maze (O-maze) test, and Open field test were used. Furthermore, the mechanism behind the neuroprotective effect of WFA in epilepsy was investigated using the transcriptomics analysis and verified on epileptic patient and epileptic mouse samples using Western blotting (WB) and immunofluorescence (IF) staining. In addition, WB, IF staining and specific antagonists/agonists were used to investigate astrocyte polarization and the regulatory signaling pathways involved. More critically, ferroptosis was assessed utilizing lipocalin-2 (LCN2) overexpression cell lines, siRNA knockdown, JC-1 staining, WB, IF staining, flow cytometry, electron microscopy (TEM), and ferroptosis-related GSH and MDA indicators. RESULTS: In this study, we observed that WFA treatment reduced the number of recurrent seizures and time in seizure, and the loss of neurons in the hippocampal area in in epileptic mice, and even improved cognitive and anxiety impairment after epilepsy in a dose depend. Furthermore, WFA treatment was proven to enhance to the transformation of post-epileptic astrocytes from neurotoxic-type A1 to A2 astrocytes in both in vivo and in vitro experiments by inhibiting the phosphoinositide 3-kinase /AKT signaling pathway. At last, transcriptomics analysis in combination with functional experimental validation, it was discovered that WFA promoted astrocyte polarity transformation and then LCN2 in astrocytes, which inhibited neuronal ferroptosis to exert neuroprotective effects after epilepsy. In addition, we discovered significant astrocytic LCN2 expression in human TLE patient hippocampal samples. CONCLUSIONS: Taken together, for the first, our findings suggest that WFA has neuroprotective benefits in epilepsy by modulating astrocyte polarization, and that LCN2 may be a novel potential target for the prevention and treatment of ferroptosis after epilepsy.

Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

Improving diagnostic confidence in low-dose dual-energy CTE with low energy level and deep learning reconstruction.

OBJECTIVE: To demonstrate the value of using 50 keV virtual monochromatic images with deep learning image reconstruction (DLIR) in low-dose dual-energy CT enterography (CTE). METHODS: In this prospective study, 114 participants (62 % M; 41.9 ± 16 years) underwent dual-energy CTE. The early-enteric phase was performed using standard-dose (noise index (NI): 8) and images were reconstructed at 70 keV and 50 keV with 40 % strength ASIR-V (ASIR-V40%). The late-enteric phase used low-dose (NI: 12) and images were reconstructed at 50 keV with ASIR-V40%, and DLIR at medium (DLIR-M) and high strength (DLIR-H). Image standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge-rise-slope (ERS) were computed. The quantitative comb sign score was calculated for the 27 patients with Crohn's disease. The subjective noise, image contrast, display of rectus artery were scored using a 5-point scale by two radiologists blindly. RESULTS: Effective dose was reduced by 50 % (P < 0.001) in the late-enteric phase to 3.26 mSv. The lower-dose 50 keV-DLIR-H images (SD:17.7 ± 0.5HU) had similar image noise (P = 0.97) as the standard-dose 70 keV-ASIR-V40% images (SD:17.7 ± 0.73HU), but with higher (P < 0.001) SNR, CNR, ERS and quantitative comb sign score (5.7 ± 0.17, 1.8 ± 0.12, 156.04 ± 5.21 and 5.05 ± 0.73, respectively). Furthermore, the lower-dose 50 keV-DLIR-H images obtained the highest score in the rectus artery visibility (4.27 ± 0.6). CONCLUSIONS: The 50 keV images in dual-energy CTE with DLIR provides high-quality images, with a 50 % reduction in radiation dose. Images with high contrast and density resolutions significantly enhance the diagnostic confidence of Crohn's disease and are essential for the clinical development of individualized treatment plans.

Knowledge, attitudes, and practices of gouty arthritis in the general population aged > 30.

BACKGROUND: A knowledge of gouty arthritis could help in the primary prevention of the disease development and lead to an early diagnosis if it occurs. This study investigated the knowledge, attitudes, and practices (KAP) toward gouty arthritis in the general population > 30 years old. METHODS: This web-based cross-sectional study was conducted among the general population > 30 years old between January and March 2023 in Chengdu, Sichuan. The questionnaire was designed by the investigators based on the available guidelines (Cronbach's α = 0.846). A score above 70% indicated good knowledge, a positive attitude, and proactive practice. Multivariable and structural equation modeling (SEM) analyses were performed to analyze the factors influencing KAP. RESULTS: A total of 537 questionnaires were included. The knowledge, attitudes, and practices scores were 13.12 ± 6.41, 25.28 ± 3.97, and 45.25 ± 5.77, respectively. Female (OR = 0.47, 95%CI: 0.31-0.71, P < 0.001), suburban living (OR = 0.18, 95%CI: 0.04-0.78, P = 0.022), heads of institution/organization and professional and technical staff (OR = 2.04, 95%CI: 1.23-3.39, P = 0.006), and an income of < 2,000 yuan (OR = 0.35, 95%CI: 0.14-0.85, P = 0.021) were independently associated with knowledge. Female (OR = 2.17, 95%CI: 1.43-3.30, P < 0.001), age (OR = 1.03, 95%CI: 1.01-1.05, P = 0.001), college and above education (OR = 2.26, 95%CI: 1.16-4.41, P = 0.017), an income of 5,000-10,000 yuan (OR = 2.05, 95%CI: 1.27-3.31, P = 0.003), and an income of > 10,000 yuan (OR = 2.07, 95%CI: 1.12-3.81, P = 0.020) were independently associated with attitudes. Attitude (OR = 1.31, 95%CI: 1.23-1.40, P < 0.001), female (OR = 1.62, 95%CI: 1.01-2.58, P = 0.044), and age (OR = 1.02, 95%CI: 1.00-1.04, P = 0.016) were independently associated with practices. The structural equation modeling analysis showed that knowledge directly influenced attitude (ß=-0.10, P < 0.001) and indirectly influenced practice (ß=-0.07, P < 0.001), and attitude directly influenced practice (ß = 0.68, P < 0.001). CONCLUSION: The general population over 30 years old had inadequate knowledge, unfavorable attitudes, and less proactive practices toward gouty arthritis. Targeted interventions should focus on enhancing knowledge about gout and promoting positive attitudes toward its management.

Acute treatment of bilateral rTMS combined with antidepressants on the plasma fatty acids for major depressive episodes.

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.