Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.

BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

[Changes of ferroptosis related pathways in hippocampus of mice exposed to high-altitude hypoxia].

The present study aimed to investigate the occurrence of ferroptosis in mouse hippocampal tissue and changes in related pathways after exposure to high-altitude hypoxia. A low-pressure hypoxia model was established using a high-altitude environment at 4 010 m. HE staining was used to observe morphological changes in mouse hippocampal tissue, immunohistochemical staining was used to observe lipid peroxidation levels in hippocampal tissue, and corresponding kits were used to measure malondialdehyde (MDA), reduced glutathione (GSH), and Fe2+ levels in hippocampal tissue. Western blot was used to detect glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), and acyl-CoA synthase long chain family member 4 (ACSL4). The results showed that, compared with the plain control group, the mice exposed to high-altitude hypoxia for 1, 3, 7, and 14 d exhibited significant pathological damage, disordered arrangement, and obvious nuclear condensation in the dentate gyrus of the hippocampus. Compared with the plain control group, high-altitude hypoxia exposure increased 4-hydroxynonenal (4-HNE) content in the dentate gyrus and hippocampal MDA content, whereas significantly decreased hippocampal GSH content. Compared with the plain control group, the Fe2+ content in the hippocampus of mice exposed to high-altitude hypoxia for 14 d significantly increased. Compared with the plain control group, the protein expression levels of GPX4, FTH1, FPN1, TfR1, and FSP1 in the hippocampus of mice exposed to high-altitude hypoxia were significantly down-regulated (SLC7A11 was significantly down-regulated only in the 7-d high-altitude hypoxia exposure group), while the protein expression level of ACSL4 was only significantly up-regulated in the 14-d high-altitude hypoxia exposure group. These results suggest that exposure to high-altitude hypoxia for 14 d can reduce GSH synthesis in mouse hippocampus, down-regulate GPX4 expression, lead to GSH metabolism disorders, inhibit iron storage and efflux, promote lipid peroxidation reaction, and inhibit CoQ10H2's anti-lipid peroxidation effect, ultimately leading to ferroptosis.

Mycoplasma pneumoniae infection outbreak in Guangzhou, China after COVID-19 pandemic.

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

SIRT1-driven mechanism: sevoflurane's interference with mESC neural differentiation via PRRX1/DRD2 cascade.

Investigating the sevoflurane-induced perturbation in the differentiation of mouse embryonic stem cells (mESCs) into neural stem cells (mNSCs), our study delineates a novel SIRT1/PRRX1/DRD2/PKM2/NRF2 axis as a key player in this intricate process. Sevoflurane treatment hindered mESC differentiation, evidenced by altered expression patterns of pluripotency and neural lineage markers. Mechanistically, sevoflurane downregulated Sirt1, setting in motion a signaling cascade. Sevoflurane may inhibit PKM2 dimerization and NRF2 signaling pathway activation by inhibiting the expression of SIRT1 and its downstream genes Prrx1 and DRD2, ultimately inhibiting mESCs differentiation into mNSCs. These findings contribute to our understanding of the molecular basis of sevoflurane-induced neural toxicity, presenting a potential avenue for therapeutic intervention in sevoflurane-induced perturbation in the differentiation of mESCs into mNSCs by modulating the SIRT1/PRRX1/DRD2/PKM2/NRF2 axis.

Isoflurane preconditioning attenuates OGD/R-induced cardiomyocyte cytotoxicity by regulating the miR-210/BNIP3 axis.

Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R-induced upregulation of miR-210, a hypoxia-responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR-210 in regulating the effects of isoflurane preconditioning on OGD/R-induced cardiomyocyte injury, AC16 cells were transfected with anti-miR-210 or control anti-miRNA. Results showed that isoflurane preconditioning attenuated OGD/R-induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK-MB levels), which could be reversed by anti-miR-210. Isoflurane preconditioning also prevented OGD/R-induced increase in apoptotic rate, caspase-3 and caspase-9 activities, and Bax level and decrease in Bcl-2 expression level, while anti-miR-210 blocked these effects. We also found that anti-miR-210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R-induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p-DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR-210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR-210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R-induced cardiac cytotoxicity by regulating the miR-210/BNIP3 axis.

Interaction between Extreme Temperature Events and Fine Particulate Matter on Cardiometabolic Multimorbidity: Evidence from Four National Cohort Studies.

Accumulating evidence linked extreme temperature events (ETEs) and fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM); however, it remained unknown if and how ETEs and PM2.5 interact to trigger CMM occurrence. Merging four Chinese national cohorts with 64,140 free-CMM adults, we provided strong evidence among ETEs, PM2.5 exposure, and CMM occurrence. Performing Cox hazards regression models along with additive interaction analyses, we found that the hazards ratio (HRs) of CMM occurrence associated with heatwave and cold spell were 1.006-1.019 and 1.063-1.091, respectively. Each 10 µg/m3 increment of PM2.5 concentration was associated with 17.9% (95% confidence interval: 13.9-22.0%) increased risk of CMM. Similar adverse effects were also found among PM2.5 constituents of nitrate, organic matter, sulfate, ammonium, and black carbon. We observed a synergetic interaction of heatwave and PM2.5 pollution on CMM occurrence with relative excess risk due to the interaction of 0.999 (0.663-1.334). Our study provides novel evidence that both ETEs and PM2.5 exposure were positively associated with CMM occurrence, and the heatwave interacts synergistically with PM2.5 to trigger CMM.

Role of legumain in metabolic dysfunction, diagnosis, and prognosis of patients with atherosclerosis.

BACKGROUND: The purpose of this study was to investigate the role of legumain in metabolic dysfunction, diagnosis, and prognosis in patients with atherosclerosis. METHODS: Plasma levels of legumain from patients with atherosclerosis (n = 320) and healthy controls (n = 320), expression of legumain in atheromatous plaque and secreted from monocyte-derived macrophages were measured using enzyme-linked-immunosorbent assay, reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and fluorescence. RESULTS: Data demonstrated that atherosclerotic patients had higher plasma level of legumain than healthy controls, which was a diagnostic and prognostic marker and corrected with the degree of atherosclerosis. It found that atheromatous plaque and endothelial cell had higher legumain expression than non-atherosclerotic arteries (controls). Legumain showed significantly increased secretion from pro-inflammatory M1 compared to pro-resolving M2 macrophages during monocyte-derived macrophages, which was localized to structures resembling foam cells. CONCLUSION: In conclusion, our data indicate that legumain expression is upregulated in both plasma and plaques of patients with atherosclerosis, which is associated with metabolic dysfunction of endothelial cell and might be a diagnostic and prognostic marker of atherosclerosis.

Effects of exposure to snus marketing with versus without modified risk tobacco product claims on snus use intention and perceived harm among young adults.

BACKGROUND: We tested whether snus marketing with modified risk tobacco product (MRTP) claims: (a) promotes accurate knowledge about snus's health effects in young adults and (b) encourages use intentions in only those who use combustible tobacco without attracting other young adult populations. METHODS: A randomised between-subjects experiment was embedded in a 2020 web survey of participants from Los Angeles (aged 19-23 years). Participants viewed mass-marketed snus advertising materials with (n=1212) vs without (n=1225) US Food and Drug Administration-authorised MRTP claims. After advertising exposure, snus use intention and perceptions of snus harms relative to cigarettes or e-cigarettes were measured. RESULTS: Advertisements with versus without MRTP claims did not affect snus use intention (18.0% vs 19.4%) but produced a higher prevalence of perceptions that snus was less harmful than cigarettes (12.6% vs 9.1%; p=0.007) and e-cigarettes (8.0% vs 5.8%; p=0.04). MRTP claim exposure effects did not differ by past 30-day e-cigarette or combustible tobacco use. Snus use intentions after marketing exposure, collapsed across MRTP claim conditions, were higher in those who did versus did not report past 30-day use of e-cigarettes (38.4% vs 14.3%; adjusted OR (95% CI) 2.95 (2.28 to 3.81); p<0.001) or combustible tobacco (44.0% vs 16.2%; adjusted OR (95% CI) 2.26 (1.62 to 3.16); p<0.001). CONCLUSION: Although some young adults who vape or smoke may have snus use intentions, snus MRTP claims might not affect young adults' snus use intentions, regardless of whether they vape/smoke. MRTP claims might modestly increase the accuracy of perceived harms of snus relative to cigarettes while also slightly causing unsubstantiated perceptions of lower harm than e-cigarettes.

Association between obstructive sleep apnea and arrhythmia and heart rate variability among hypertensive patients.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and the occurrence of arrhythmias and heart rate variability (HRV) in hypertensive patients is not elucidated. Our study investigates the association between OSA, arrhythmias, and HRV in hypertensive patients. METHODS: We conducted a cross-sectional analysis involving hypertensive patients divided based on their apnea-hypopnea index (AHI) into two groups: the AHI ≤ 15 and the AHI > 15. All participants underwent polysomnography (PSG), 24-hour dynamic electrocardiography (DCG), cardiac Doppler ultrasound, and other relevant evaluations. RESULTS: The AHI > 15 group showed a significantly higher prevalence of frequent atrial premature beats and atrial tachycardia (P = 0.030 and P = 0.035, respectively) than the AHI ≤ 15 group. Time-domain analysis indicated that the standard deviation of normal-to-normal R-R intervals (SDNN) and the standard deviation of every 5-minute normal-to-normal R-R intervals (SDANN) were significantly higher in the AHI > 15 group (P = 0.020 and P = 0.033, respectively). Frequency domain analysis revealed that the low-frequency (LF), high-frequency (HF) components, and the LF/HF ratio were also significantly elevated in the AHI > 15 group (P < 0.001, P = 0.031, and P = 0.028, respectively). Furthermore, left atrial diameter (LAD) was significantly larger in the AHI > 15 group (P < 0.001). Both univariate and multivariable linear regression analyses confirmed a significant association between PSG-derived independent variables and the dependent HRV parameters SDNN, LF, and LF/HF ratio (F = 8.929, P < 0.001; F = 14.832, P < 0.001; F = 5.917, P = 0.016, respectively). CONCLUSIONS: Hypertensive patients with AHI > 15 are at an increased risk for atrial arrhythmias and left atrial dilation, with HRV significantly correlating with OSA severity.

Spatial distribution of cable bacteria in nationwide organic-matter-polluted urban rivers in China.

An overload of labile organic matter triggers the water blackening and odorization in urban rivers, leading to a unique microbiome driving biogeochemical cycles in these anoxic habitats. Among the key players in these environments, cable bacteria interfere directly with C/N/S/O cycling, and are closely associated with phylogenetically diverse microorganisms in anoxic sediment as an electron conduit to mediate long-distance electron transport from deep-anoxic-layer sulfide to oxic-layer oxygen. Despite their hypothesized importance in black-odorous urban rivers, the spatial distribution patterns and roles of cable bacteria in large-scale polluted urban rivers remain inadequately understood. This study examined the diversity and spatial distribution pattern of cable bacteria in sediment samples from 186 black-odorous urban rivers across China. Results revealed the co-existence of two well-characterized cable bacteria (i.e., Candidatus Electrothrix and Candidatus Electronema), with Candidatus Electrothrix exhibiting a comparatively wider distribution in the polluted urban rivers. Concentrations of DOC, SS, sulfate, nitrate, and heavy metals (e.g., Ni and Cr) were correlated with the cable bacteria diversity, indicating their essential role in biogeochemical cycles. The activation energy of cable bacteria was 0.624 eV, close to the canonical 0.65 eV. Furthermore, cable bacteria were identified as key connectors and module hubs, closely associated with denitrifiers, sulfate-reducing bacteria, methanogens and alkane degraders, highlighting their role as keystone functional lineages in the contaminated urban rivers. Our study provided the first large-scale and comprehensive insight into the cable bacteria diversity, spatial distribution, and their essential function as keystone species in organic-matter-polluted urban rivers.

Protective Effect and Related Mechanism of Modified Danggui Buxue Decoction on Retinal Oxidative Damage in Mice based on Network Pharmacology.

INTRODUCTION: Age-related macular degeneration (AMD) is one of the common diseases that cause vision loss in the elderly, and oxidative stress has been considered a major pathogenic factor for AMD. Modified Danggui Buxue Decoction (RRP) has a good therapeutic effect on non-proliferatic diabetic retinopathy and can improve the clinical symptoms of patients. AIM: This study aimed to predict and verify the protective effect and mechanism of RRP on retinal oxidative damage in mice based on network pharmacology and animal experiments. METHODS: A total of 15 key active components included in RRP interacted with 57 core targets related to retinal oxidative damage (such as AKT1, NFE2L2, HMOX1), mainly involved in the AGE-RAGE signaling pathway in diabetic complications, PI3K-AKT signaling pathway and so on. Further studies in vivo found that RRP improved the retinal oxidative damage, increased the content of SOD and GSH, decreased the content of MDA in mouse serum, promoted the expression of p-PI3K, p-AKT, Nrf2, HO-1 and NQO1 proteins in the mouse retina, and inhibited the expression of Nrf2 in the cytoplasm. RESULTS: This study revealed that RRP had a protective effect on oxidative damage of the retina in mice, and might exert anti-oxidative effect by activating the PI3K/Akt/Nrf2 signal pathway. CONCLUSION: This study provided scientific data for the further development of hospital preparations of RRP, and a good theoretical basis for the clinical application of RRP.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Effects of taurine on metabolomics of bovine mammary epithelial cells under high temperature conditions.

High temperature induces heat stress, adversely affecting the growth and lactation performance of cows. Research has shown the protective effect of taurine against hepatotoxicity both in vivo and in vitro. This study aimed to investigate the effect of taurine on the metabolomics of mammary epithelial cells of dairy cows under high-temperature conditions. Mammary epithelial cells were exposed to 0 mmol/L (HS, control), 8 mmol/L (HT-8), and 32 mmol/L (HT-32) of taurine, then incubated at 42°C for 6 h. Metabolomics analysis was conducted using Liquid Chromatograph Mass Spectrometer (LC-MS). Compared with the HS group, 2,873 and 3,243 metabolites were detected in the HT-8 group in positive and negative ion modes. Among these, 108 and 97 metabolites were significantly upregulated in positive and negative ion modes, while 60 and 166 metabolites were downregulated. Notably, 15 different metabolites such as palmitic acid, adenine and hypoxanthine were screened out in the HT-8 group. Compared with the HS group, 2,873 and 3,243 metabolites were, respectively, detected in the HT-32 group in the positive and negative ion modes. Among those metabolites, 206 metabolites were significantly up-regulated, while 206 metabolites were significantly downregulated in the positive mode. On the other hand, 497 metabolites were significantly upregulated in the negative mode, while 517 metabolites were reported to be downregulated. Noteworthy, 30 distinct metabolites, such as palmitic acid, phytosphingosine, hypoxanthine, nonanoic acid, and octanoic acid, were screened out in the HT-32 group. KEGG enrichment analysis showed that these metabolites were mainly involved in lipid metabolism, purine metabolism and other biological processes. Overall, our study indicates that taurine supplementation alters the metabolites primarily associated with purine metabolism, lipid metabolism and other pathways to alleviate heat stress in bovine mammary epithelial cells.

The study of the relationship between moderate to severe sleep obstructive apnea and cognitive impairment, anxiety, and depression.

Objective: The present study endeavored to investigate the interconnection between obstructive sleep apnea (OSA) and cognitive function, alongside the manifestations of depression and anxiety. Simultaneously, an analysis was conducted to discern the factors exerting influence upon cognitive function. Methods: A cohort of 102 patients, who had undergone polysomnography (PSG) at Binhu Hospital, Anhui Medical University, between January 2022 and June 2023, was encompassed in the study. Employing the PSG findings, these individuals were classified into two distinct categories: the grouping consisted of those with either negligible or mild OSA, and the other comprised individuals with moderate to severe OSA. Utilizing the Montreal Cognitive Assessment (MoCA-Beijing), Stroop Color and Word Test (SCWT), Digit Span Test (DST), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), scores were recorded and analysed for each of the respective assessments. Additionally, discrepancies and associations between these groups were also scrutinized. Results: The group exhibiting moderate to severe OSA demonstrated significantly elevated measurements in parameters such as neck circumference, BMI, completion times for SCWT-A, B, C, Sleep Inefficiency Index (SIE), SAS, and SDS, in comparison to the No or Mild OSA group. Furthermore, the moderate-severe OSA group manifested notably diminished MoCA scores in areas of visual-spatial and executive function, memory, language, abstraction, delayed recall, orientation, total MoCA score, lowest oxygen saturation (LSaO2), average oxygen saturation, Digit Span Test-backward(DST-b), and Digit Span Test-forward(DST-f), as contrasted with the no-mild OSA group. These inter-group disparities exhibited statistical significance (p < 0.05). The MoCA total score portrayed inverse correlations with age, Apnea-Hypopnea Index (AHI), BMI, SIE, SAS, SDS, CT90%, AHT90%, and Hypoxic Apnea Duration (HAD) (ranging from -0.380 to -0.481, p < 0.05). Conversely, it displayed positive correlations with DST-f, DST-b, LSaO2, and average oxygen saturation (ranging from 0.414 to 0.744, p < 0.05). Neck circumference, AHI, and SAS were autonomously linked to MoCA scores (OR = 1.401, 1.028, 1.070, p < 0.05), while AHI exhibited an independent correlation with SDS and SAS scores (OR = 1.001, p = 0.003). Conclusion: Patients grappling with moderate to severe OSA frequently reveal cognitive impairment and concomitant emotional predicaments encompassing depression and anxiety. These manifestations share an intimate association with AHI, LSaO2, and average oxygen saturation. Notably, anxiety, when coupled with OSA, emerges as an autonomous influential element impinging upon cognitive impairment.

Unraveling the important role of comammox Nitrospira to nitrification in the coastal aquaculture system.

Increasing nitrogen (N) input to coastal ecosystems poses a serious environmental threat. It is important to understand the responses and feedback of N removal microbial communities, particularly nitrifiers including the newly recognized complete ammonia-oxidizers (comammox), to improve aquaculture sustainability. In this study, we conducted a holistic evaluation of the functional communities responsible for nitrification by quantifying and sequencing the key functional genes of comammox Nitrospira-amoA, AOA-amoA, AOB-amoA and Nitrospira-nxrB in fish ponds with different fish feeding levels and evaluated the contribution of nitrifiers in the nitrification process through experiments of mixing pure cultures. We found that higher fish feeding dramatically increased N-related concentration, affecting the nitrifying communities. Compared to AOA and AOB, comammox Nitrospira and NOB were more sensitive to environmental changes. Unexpectedly, we detected an equivalent abundance of comammox Nitrospira and AOB and observed an increase in the proportion of clade A in comammox Nitrospira with the increase in fish feeding. Furthermore, a simplified network and shift of keystone species from NOB to comammox Nitrospira were observed in higher fish-feeding ponds. Random forest analysis suggested that the comammox Nitrospira community played a critical role in the nitrification of eutrophic aquaculture ponds (40-70 µM). Through the additional experiment of mixing nitrifying pure cultures, we found that comammox Nitrospira is the primary contributor to the nitrification process at 200 µM ammonium. These results advance our understanding of nitrifying communities and highlight the importance of comammox Nitrospira in driving nitrification in eutrophic aquaculture systems.

Physician and Artificial Intelligence Chatbot Responses to Cancer Questions From Social Media.

Importance: Artificial intelligence (AI) chatbots pose the opportunity to draft template responses to patient questions. However, the ability of chatbots to generate responses based on domain-specific knowledge of cancer remains to be tested. Objective: To evaluate the competency of AI chatbots (GPT-3.5 [chatbot 1], GPT-4 [chatbot 2], and Claude AI [chatbot 3]) to generate high-quality, empathetic, and readable responses to patient questions about cancer. Design, Setting, and Participants: This equivalence study compared the AI chatbot responses and responses by 6 verified oncologists to 200 patient questions about cancer from a public online forum. Data were collected on May 31, 2023. Exposures: Random sample of 200 patient questions related to cancer from a public online forum (Reddit r/AskDocs) spanning from January 1, 2018, to May 31, 2023, was posed to 3 AI chatbots. Main Outcomes and Measures: The primary outcomes were pilot ratings of the quality, empathy, and readability on a Likert scale from 1 (very poor) to 5 (very good). Two teams of attending oncology specialists evaluated each response based on pilot measures of quality, empathy, and readability in triplicate. The secondary outcome was readability assessed using Flesch-Kincaid Grade Level. Results: Responses to 200 questions generated by chatbot 3, the best-performing AI chatbot, were rated consistently higher in overall measures of quality (mean, 3.56 [95% CI, 3.48-3.63] vs 3.00 [95% CI, 2.91-3.09]; P < .001), empathy (mean, 3.62 [95% CI, 3.53-3.70] vs 2.43 [95% CI, 2.32-2.53]; P < .001), and readability (mean, 3.79 [95% CI, 3.72-3.87] vs 3.07 [95% CI, 3.00-3.15]; P < .001) compared with physician responses. The mean Flesch-Kincaid Grade Level of physician responses (mean, 10.11 [95% CI, 9.21-11.03]) was not significantly different from chatbot 3 responses (mean, 10.31 [95% CI, 9.89-10.72]; P > .99) but was lower than those from chatbot 1 (mean, 12.33 [95% CI, 11.84-12.83]; P < .001) and chatbot 2 (mean, 11.32 [95% CI, 11.05-11.79]; P = .01). Conclusions and Relevance: The findings of this study suggest that chatbots can generate quality, empathetic, and readable responses to patient questions comparable to physician responses sourced from an online forum. Further research is required to assess the scope, process integration, and patient and physician outcomes of chatbot-facilitated interactions.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Influence of rice husk ash on the mechanical properties of ultra-high strength engineered cementitious composites (UHS-ECC).

Generally, UHS-ECC should consume massive cement, which is negative to its sustainability as cement production leads to 8% of global CO2 emissions. To decrease the cost of production and carbon emissions of UHS-ECC, rice husk ash was employed to replace the cement as a supplementary cementitious material in this study. Experiment results illustrate that blending rice husk ash (RHA) would decrease the fluidity of mortar. Furthermore, the green UHS-ECC shows a maximum compressive strength of 130.3 MPa at 28 days when RHA content was 20% of cement. The ultimate tensile strength of UHS-ECCs first increased and then decreased, while both tensile strain and strain energy presented an opposite tendency. At the micro-scale, if RHA content was lower than 20% of cement, incorporating RHA can significantly decreasing fiber bridging complementary energy of UHS-ECC, thus reducing pseudo strain hardening energy (PSHenergy) index, which finely agrees with the degradation of ductility of UHS-ECCs. To guarantee the features of ultra-high strength, acceptable workability, and high tensile ductility, the RHA dosage should not be in excess 20% of cement. These researched results are prospected to the contribution of pozzolanic RHA on the efficient usage of sustainable UHS-ECC.

The clinical manifestations and molecular pathogenesis of radiation fibrosis.

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.