Implementing a completely autotrophic nitrogen removal over nitrite process using a novel umbrella basalt fiber carrier.

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L-1, and the dissolved oxygen was controlled below 0.8 mg L-1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Silicon photocathode functionalized with osmium complex catalyst for selective catalytic conversion of CO2 to methane.

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s-1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching -14.11 mA cm-2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Conversion of Propargylic Amines with CO2 Catalyzed by a Highly Stable Copper(I) Iodide Thorium-Based Heterometal-Organic Framework.

The conversion of CO2 to generate high-value-added chemicals has become one of the hot research topics in green synthesis. Thereinto, the cyclization reaction of propargylic amines with CO2 is highly attractive because the resultant oxazolidinones are widely found in pharmaceutical chemistry. Cu(I)-based metal-organic frameworks (MOFs) as catalysts exhibit promising application prospects for CO2 conversion. However, their practical application was greatly limited due to Cu(I) being liable to disproportionation or oxidization. Herein, the solid copper(I) iodide thorium-based porous framework {[Cu5I6Th6(µ3-O)4(µ3-OH)4(H2O)10(L)10]·OH·4DMF·H2O}n (1) (HL = 2-methylpyridine-4-carboxylic acid) constructed by [Th6] clusters and [CuxIy] subunits was successfully prepared and structurally characterized. To our knowledge, this is the first copper(I) iodide-based actinide organic framework. Catalytic investigations indicate that 1 can effectively catalyze the cyclization of propargylic amines with CO2 under ambient conditions, which can be reused at least five times without a remarkable decline of catalytic activity. Importantly, 1 exhibits excellent chemical stability and the oxidation state of Cu(I) in it can remain stable under various conditions. This work can provide a valuable strategy for the synthesis of stable Cu(I)-MOF materials.

Sleep Deprivation Induces Gut Damage via Ferroptosis.

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.

[Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase].

Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

A Novel Method for Preparing Lightweight and High-Strength Ceramisite Coarse Aggregates from Solid Waste Materials.

A novel method is introduced in this study for producing ceramisite coarse aggregates that are both lightweight and possess high strength. The process involves utilizing fly ash as the primary material, along with coal ash floating beads (CAFBs) that have high softening temperature and a spherical hollow structure serving as the template for forming pores. This study examined the impact of varying particle size and quantity of floating beads on the composition and characteristics of ceramisite aggregates. Results showed that the high softening temperature of floating beads provided stability to the spherical cavity structure throughout the sintering process. Furthermore, the pore structure could be effectively tailored by manipulating the size and quantity of the floating beads in the manufacturing procedure. The obtained ceramisite aggregates feature a compact outer shell and a cellular inner core with uniformly distributed pores that are isolated from each other and mostly spherical in form. They achieve a low density ranging from 723 to 855 kg/m3, a high cylinder compressive strength between 8.7 and 13.5 MPa, and minimal water absorption rates of 3.00 to 4.09%. The performance metrics of these coarse aggregates significantly exceeded the parameters specified in GB/T 17431.1-2010 standards.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Boosting PRRSV-Specific Cellular Immunity: The Immunological Profiling of an Fc-Fused Multi-CTL Epitope Vaccine in Mice.

The continuously evolving PRRSV has been plaguing pig farms worldwide for over 30 years, with conventional vaccines suffering from insufficient protection and biosecurity risks. To address these challenges, we identified 10 PRRSV-specific CTL epitopes through enzyme-linked immunospot assay (ELISPOT) and constructed a multi-epitope peptide (PTE) by linking them in tandem. This PTE was then fused with a modified porcine Fc molecule to create the recombinant protein pFc-PTE. Our findings indicate that pFc-PTE effectively stimulates PRRSV-infected specific splenic lymphocytes to secrete high levels of interferon-gamma (IFN-γ) and is predicted to be non-toxic and non-allergenic. Compared to PTE alone, pFc-PTE not only induced a comparable cellular immune response in mice but also extended the duration of the immune response to at least 10 weeks post-immunization. Additionally, pFc-PTE predominantly induced a Th1 immune response, suggesting its potential advantage in enhancing cellular immunity. Consequently, pFc-PTE holds promise as a novel, safe, and potent candidate vaccine for PRRSV and may also provide new perspectives for vaccine design against other viral diseases.

Progressive Ataxia due to de novo Missense Variants in the CACNA1A Gene.

The CACNA1A gene encodes the alpha-1A subunit of P/Q type voltage-gated calcium channel Cav2.1, which is associated with a broad clinical spectrum and variable symptomatology. While few patients with progressive ataxia caused by CACNA1A missense variants have been reported, here we report three unrelated Chinese patients with progressive ataxia due to de novo missense variants in the CACNA1A gene, including a novel pathogenic variant (c.4999C > G) and a previously reported pathogenic variant (c.4037G > A). Our findings and a systematic literature review show the unique phenotype of progressive ataxia caused by missense variants and enlarge the genetic and clinical spectrum of CACNA1A. This suggests that in addition to routine screening for dynamic mutations, screening for CACNA1A variants is important for clinicians facing patients with progressive ataxia.

Global research status and trends of enteric glia: a bibliometric analysis.

Background: Enteric glia are essential components of the enteric nervous system. Previously believed to have a passive structural function, mounting evidence now suggests that these cells are indispensable for maintaining gastrointestinal homeostasis and exert pivotal influences on both wellbeing and pathological conditions. This study aimed to investigate the global status, research hotspots, and future directions of enteric glia. Methods: The literature on enteric glia research was acquired from the Web of Science Core Collection. VOSviewer software (v1.6.19) was employed to visually represent co-operation networks among countries, institutions, and authors. The co-occurrence analysis of keywords and co-citation analysis of references were conducted using CiteSpace (v6.1.R6). Simultaneously, cluster analysis and burst detection of keywords and references were performed. Results: A total of 514 publications from 36 countries were reviewed. The United States was identified as the most influential country. The top-ranked institutions were University of Nantes and Michigan State University. Michel Neunlist was the most cited author. "Purinergic signaling" was the largest co-cited reference cluster, while "enteric glial cells (EGCs)" was the cluster with the highest number of co-occurring keywords. As the keyword with the highest burst strength, Crohns disease was a hot topic in the early research on enteric glia. The burst detection of keywords revealed that inflammation, intestinal motility, and gut microbiota may be the research frontiers. Conclusion: This study provides a comprehensive bibliometric analysis of enteric glia research. EGCs have emerged as a crucial link between neurons and immune cells, attracting significant research attention in neurogastroenterology. Their fundamental and translational studies on inflammation, intestinal motility, and gut microbiota may promote the treatment of some gastrointestinal and parenteral disorders.

Facet-switching of rate-determining step on copper in CO2-to-ethylene electroreduction.

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone.

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

Effects of intra-operative magnesium sulfate infusion on orthognathic surgery: A prospective and randomized controlled trial.

Purpose: To comprehensively understand the effects of intra-operative infusion of magnesium sulfate on patients who underwent orthognathic surgery, including remifentanil consumption, postoperative pain, postoperative nausea and vomiting (PONV), inflammatory response, and serum magnesium levels. Methods: Seventy-five adult patients undergoing orthognathic surgery under general balanced anesthesia were randomly divided into two groups. One group (Group M) received 50 mg/kg of magnesium sulfate in 20 mL 0.9 % saline after intubation, followed by a continuous infusion at a rate of 15 mg/kg/h until 30 min before the anticipated end of surgery. The other group (Group C) received an equal volume of isotonic saline as a placebo. (Clinical trial registration number: chiCTR2100045981). Results: The primary outcome was remifentanil consumption. The secondary outcomes included the pain score assessed using the verbal numerical rating scale (VNRS) and PONV assessed using a Likert scale. Remifentanil comsumption in Group M was lower than Group C (mean ± SD: 0.146 ± 0.04 µg/kg/min vs. 0.173 ± 0.04 µg/kg/min, P = 0.003). At 2 h after surgery, patients in Group C suffered more severe PONV than those in Group M (median [interquartile range, IQR]: 1 [3] vs. 1 [0], mean rank: 31.45 vs. 42.71, P = 0.040). At post-anesthesia care unit (PACU), postoperative pain in Group C was severe than Group M (3 [1] vs. 3 [0], mean rank: 31.45 vs. 42.71, P = 0.013). Changes in haemodynamics and surgical field scores did not differ between the groups (all P > 0.05). The levels of cytokines (IL-4, IL-6, IL-8, IL-10, TNF-a, and MIP-1ß) were not significantly different between the groups after surgery (all P > 0.05). Postoperative serum magnesium levels in Group C were lower than those in Group M (0.74 ± 0.07 mmol/L vs. 0.91 ± 0.08 mmol/L, P = 0.000) and the preoperative level (0.74 ± 0.07 mmol/L vs. 0.83 ± 0.06 mmol/L, P = 0.219). Conclusions: In orthognathic surgery, magnesium sulfate administration can reduce remifentanil requirement and relieve PONV and postoperative pain in the early postoperative phase.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.