Modulation of cyclophosphamide-induced immunosuppression and intestinal flora in broiler by deep eutectic solvent extracted polysaccharides of Acanthopanax senticosus.

Introduction: The aim of this experiment was to investigate the modulation effect of Acanthopanax senticosus polysaccharide (ASPS-PD) extracted with deep eutectic solvent on cyclophosphamide-induced immunosuppression in broilers and its modulation of the gut microbiota of broilers. Methods: The 108 one-day-old broilers were divided into six groups, including the control group, the Cyclophosphamide (CY) model group, the ASPS-PD control group, the ASPA-PD high and low dose groups and the Astragalus polysaccharide group. Body weight, feed intake, feed conversion ratio, and immune organ index of broilers at 7, 14, and 21 days were determined; IL-2, IFN-γ, and lgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA); Broiler caeca feces were analyzed by amplification and 16S rRNA sequencing. Results: The results showed that ASPS-PD can restore growth performance, increase immune organ index and improve serum cytokine levels of IL-2 and IFN-γ and immunoglobulin lgG1 levels in CY-treated broilers. The analysis of cecum flora showed that ASPS-PD can promote the proliferation of beneficial bacteria and reduce the number of harmful bacteria, regulating intestinal flora. Discussion: Therefore, ASPA-PD may be a potential novel immunomodulator to ameliorate CY-induced immunosuppression and intestinal flora dysregulation in broiler.

Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial.

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.

Prebiotic characteristics of degraded polysaccharides from Acanthopanax senticosus polysaccharide on broilers gut microbiota based on in vitro digestion and fecal fermentation.

This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by H2O2-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.

Prevalence and Risk Factors Associated with Feline Infectious Peritonitis (FIP) in Mainland China between 2008 and 2023: A Systematic Review and Meta-Analysis.

To evaluate the overall prevalence of FIP infection in cats in mainland China and associated risk factors, studies on the prevalence of FIP conducted from 1 January 2008 to 20 December 2023 were retrieved from five databases-CNKI, Wanfang, PubMed, Web of Science, and ScienceDirect-and comprehensively reviewed. The 21 studies selected, with a total of 181,014 samples, underwent a rigorous meta-analysis after quality assessment. The results revealed a 2% prevalence of FIP (95% CI: 1-2%) through the random-effects model, showing considerable heterogeneity (I2 = 95.2%). The subsequent subgroup analysis revealed that the age and gender of cats are significant risk factors for FIP infection in mainland China. In order to effectively reduce and control the prevalence of FIP on the Chinese mainland, we suggest improving the immunity of cats, with special attention given to health management in kittens and intact cats, and continuously monitoring FIPV.

Autonomous Atmospheric Water Harvesting over a Wide RH Range Enabled by Super Hygroscopic Composite Aerogels.

Sorption-based atmospheric water harvesting (SAWH) offers a sustainable strategy to address the global freshwater shortage. However, obtaining sorbents with excellent performance over a wide relative humidity (RH) range and devices with fully autonomous water production remains challenging. Herein, magnesium chloride (MgCl2) is innovatively converted into super hygroscopic magnesium complexes(MC), which can effectively solve the problems of salt deliquescence and agglomeration. The MC are then integrated with photothermal aerogels composed of sodium alginate and carbon nanotubes (SA/CNTs) to form composite aerogels, which showed high water uptake over a wide RH range, reaching 5.43 and 0.27 kg kg-1 at 95% and 20% RH, respectively. The hierarchical porous structure enables the as-prepared SA/CNTs/MC to exhibit rapid absorption/desorption kinetics with 12 cycles per day at 70% RH, equivalent to a water yield of 10.0 L kg-1 day-1. To further realize continuous and practical freshwater production, a fully solar-driven autonomous atmospheric water generator is designed and constructed with two SA/CNTs/MC-based absorption layers, which can alternately conduct the water absorption/desorption process without any other energy consumption. The design provides a promising approach to achieving autonomous, high-performance, and scalable SAWH.

Eriocalyxin B alleviated ischemic cerebral injury by limiting microglia-mediated excessive neuroinflammation in mice.

Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1ß, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.

Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.

Advanced Cooling Textiles: Mechanisms, Applications, and Perspectives.

High-temperature environments pose significant risks to human health and safety. The body's natural ability to regulate temperature becomes overwhelmed under extreme heat, leading to heat stroke, dehydration, and even death. Therefore, the development of effective personal thermal-moisture management systems is crucial for maintaining human well-being. In recent years, significant advancements have been witnessed in the field of textile-based cooling systems, which utilize innovative materials and strategies to achieve effective cooling under different environments. This review aims to provide an overview of the current progress in textile-based personal cooling systems, mainly focusing on the classification, mechanisms, and fabrication techniques. Furthermore, the challenges and potential application scenarios are highlighted, providing valuable insights for further advancements and the eventual industrialization of personal cooling textiles.

Case report: 177Lu DOTA-TATE: a new scheme for the treatment of prostate neuroendocrine cancer.

Background: Most instances of small cell carcinoma originate from the lungs, while the gastrointestinal tract serves as a secondary site. Only a minuscule proportion of cases manifest within the urogenital system. Prostate small cell carcinoma (SCCP) represents an exceedingly uncommon pathological subtype within the realm of prostate cancer, displaying significant rarity in clinical settings. This scarcity has resulted in a paucity of adequate foundational and clinical research for SCCP treatment. While investigations have unveiled a certain therapeutic efficacy of radiotherapy and chemotherapy for SCCP, clinical practice has revealed suboptimal treatment outcomes. We hereby present a case report detailing the utilization of 177Lu-DOTA-TATE in the treatment of SCCP, aiming to investigate the therapeutic efficacy of 177Lu-DOTA-TATE for SCCP. Case presentation: A male patient in his 80s presented with elevated prostate-specific antigen (PSA) levels and underwent a biopsy that revealed prostate adenocarcinoma. The patient received CAB (bicalutamide + goserelin) therapy. One year later, disease progression was detected, and a second biopsy confirmed the presence of prostate small cell carcinoma. Following the diagnosis of prostate small cell carcinoma, the patient underwent two cycles of 177Lu-DOTA-TATE treatment. Subsequent to the treatment, the original lesions showed shrinkage, metastatic lesions disappeared, and there was significant improvement, approaching complete remission. Conclusion: SCCP exhibits a high degree of malignancy and aggressive invasiveness, currently lacking effective therapeutic modalities. The treatment course of this patient serves as compelling evidence for the efficacy of 177Lu-DOTA-TATE in managing SCCP, thereby opening new avenues for future SCCP treatments.

[A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites]. / æ–°ç”Ÿå„¿æœŸèµ·ç— ä¼´è¡€æ€§è ¹æ°´çš„â 型高脂蛋白血症1例.

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

Study on Matrix Damage and Control Methods of Fracturing Fluid on Tight Sandstone Gas Reservoirs.

Hydraulic fracturing is a highly effective method for stimulating the development of gas reservoirs. However, the process of pumping fracturing fluid (FF) into the reservoir unavoidably causes damage to the surrounding matrix, leading to a decrease in the overall stimulation effect. To assess the extent of matrix permeability damage caused by the intrusion of FF, as well as its impact on the pore throat structure, and to propose appropriate measures to control this damage, we conducted a series of experimental studies on tight gas reservoirs. These studies included mercury intrusion, core flow, nitrogen adsorption, linear expansion, and contact angle measurements. The findings revealed that the damage inflicted on matrix permeability by FF was significantly greater than that caused by its gel-breaking counterpart. Surprisingly, the damage rate of the rejecting fluid to the matrix was found to be comparable to that of its gel-breaking counterpart. The fractal dimension (D2) was observed to have a strong correlation with surface area, pore volume, and mean pore size, making it an effective means of characterizing pore structure characteristics. After the rock samples were displaced by the formation water, the D2 value decreased, leading to a decrease in the complexity of the pore throat structure and an increase in matrix permeability. Conversely, the displacement of the FF increased the D2 value, indicating a gradual complication of the pore throat structure and a more uneven distribution of pore sizes. The inclusion of polyamide in antiexpansion FF, as well as its gel-breaking counterpart, proved to be effective in inhibiting the hydration and expansion of clay minerals, thereby reducing water-sensitive damage. Additionally, the use of surfactants with low surface tension enhanced the flowback rate of FF by increasing the contact angle and reducing the work of adhesion. This, in turn, helped to decrease the apparent water film thickness and expand gas flow channels, ultimately improving gas permeability.

Radiomic features from multiparametric magnetic resonance imaging predict molecular subgroups of pediatric low-grade gliomas.

BACKGROUND: We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI. METHODS: 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation. RESULTS: We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set. CONCLUSIONS: The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov (NCT04217018).

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Seryl-tRNA Synthetase Shows a Noncanonical Activity of Upregulating Laccase Transcription in Trametes hirsuta AH28-2 Exposed to Copper Ion.

The function of Seryl-tRNA synthetase in fungi during gene transcription regulation beyond translation has not been reported. Here, we report a seryl-tRNA synthetase, ThserRS, which can negatively regulate laccase lacA transcription in Trametes hirsuta AH28-2 under exposure to copper ion. ThserRS was obtained through yeast one-hybrid screening using a bait sequence of lacA promoter (-502 to -372 bp). ThserRS decreased while lacA increased at the transcription level in T. hirsuta AH28-2 in the first 36 h upon CuSO4 induction. Then, ThserRS was upregulated, and lacA was downregulated. ThserRS overexpression in T. hirsuta AH28-2 resulted in a decrement in lacA transcription and LacA activity. By comparison, ThserRS silencing led to increased LacA transcripts and activity. A minimum of a 32-bp DNA fragment containing two putative xenobiotic response elements could interact with ThserRS, with a dissociation constant of 919.9 nM. ThserRS localized in the cell cytoplasm and nucleus in T. hirsuta AH28-2 and was heterologously expressed in yeast. ThserRS overexpression also enhanced mycelial growth and oxidative stress resistance. The transcriptional level of several intracellular antioxidative enzymes in T. hirsuta AH28-2 was upregulated. Our results demonstrate a noncanonical activity of SerRS that acts as a transcriptional regulation factor to upregulate laccase expression at an early stage after exposure to copper ions. IMPORTANCE Seryl-tRNA synthetase is well known for the attachment of serine to the corresponding cognate tRNA during protein translation. In contrast, its functions beyond translation in microorganisms are underexplored. We performed in vitro and cell experiments to show that the seryl-tRNA synthetase in fungi with no UNE-S domain at the carboxyl terminus can enter the nucleus, directly interact with the promoter of the laccase gene, and negatively regulate the fungal laccase transcription early upon copper ion induction. Our study deepens our understanding of the Seryl-tRNA synthetase noncanonical activities in microorganisms. It also demonstrates a new transcription factor for fungal laccase transcription.

Role of N6-methyladenosine RNA modification in gastric cancer.

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research.

Mitigation of heat stress in wheat (Triticum aestivum L.) via regulation of physiological attributes using sodium nitroprusside and gibberellic acid.

Heat stress poses a threat to plants in arid and semiarid regions, leading to soil salinization and plant mortality. Researchers are exploring remedies to alleviate these effects, including using gibberellic acid (GA3) to regulate plant enzymes and antioxidants. Additionally, sodium nitroprusside (SNP) is gaining attention, but its combined effect with GA3 requires further research. To address this gap, we investigated the effects of GA3 and SNP on plants under heat stress conditions. For that, wheat plants were cultivated under 40 °C for 6 h per day (15 days). Sodium nitroprusside (donor of NO and SNP) and gibberellic acid (GA3), respectively, with 100 µM and 5 µg/ml concentrations, were applied as foliar sprays at 10 days after sowing (DAS). Results showed that SNP + GA3 treatment had the highest plant height (4.48% increase), plant fresh weight (29.7%), plant dry weight (87%), photosynthetic rate (39.76%) and stomatal conductance (38.10%), and Rubisco (54.2%) compared to the control. Our findings indicate a significant increase in NO, H2O2, TBARS, SOD, POD, APX, proline, GR, and GB that greatly scavenged reactive oxygen species (ROS) for decreasing the adverse effect of stress. Such findings confirmed the efficacy of the combined treatment of SNP + GA3 under high-temperature stress compared to the solitary application of GA3, SNP, and control. In conclusion, using SNP + GA3 is a better strategy for mitigating heat stress in wheat than individual applications. Further research is recommended to validate the effectiveness of SNP + GA3 in other cereal crops.

Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases. METHODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged≥12 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging. RESULTS: Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was -4.2 (0.7) (95% CI -5.5, -2.8). Rate of decline in ppFVC in pamrevlumab-treated patients was slower than observed in historical published trials of non-ambulatory patients. MISSION participants experienced slower-than-anticipated muscle function declines compared with natural history and historical published trials of non-ambulatory patients with DMD. Pamrevlumab was well-tolerated. Treatment-emergent adverse events were mild to moderate, and none led to study discontinuation. CONCLUSIONS: nti-CTGF therapy with pamrevlumab represents a potential treatment for DMD. The lack of internal control group limits the results.

Opioids increase the risk of delirium in critically ill patients: A propensity score analysis.

BACKGROUND: Medications are biologically plausible and potentially modifiable risk factors for delirium. Therapies for delirium might involve more specific strategies such as avoiding the use of delirium-inducing drugs to reduce the incidence of delirium. The association between opioid exposure within 24 hours prior to delirium assessment and the risk of delirium was studied. MATERIALS AND METHODS: Using three large databases, the MIMIC III v1.4, MIMIC-IV v0.4 and eICU Collaborative Research, we performed a multicenter, observational cohort study with two cohorts to estimate the relative risks of outcomes among patients administered opioids within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1 : 1 matched cohort and to identify potential prognostic factors. The outcomes included mortality, length of intensive care unit (ICU) stay, length of hospitalization, and odds of being discharged home. RESULTS: Propensity matching successfully balanced the covariates for the 9,529 patients in each group. Opioid use was associated with a significantly higher risk for delirium than not using opioids (p < 0.001). Additionally, treatment with opioids was associated with higher mortality and a longer ICU stay (p < 0.001) than treatment without opioids. However, patients treated with opioids were more likely to be discharged home (p < 0.001). CONCLUSION: Opioids may be an independent risk factor for delirium in critically ill patients.

N, S Co-Coordinated Zinc Single-Atom Catalysts for N-Alkylation of Aromatic Amines with Alcohols: The Role of S-Doping in the Reaction.

S-doping emerged as a promising approach to further improve the catalytic performance of carbon-based materials for organic synthesis. Herein, a facile and gram-scale strategy was developed using zeolitic imidazole frameworks (ZIFs) as a precursor for the fabrication of the ZIF-derived N, S co-doped carbon-supported zinc single-atom catalyst (CNS@Zn1-AA) via the pyrolysis of S-doped ZIF-8, which was modified by aniline, ammonia and thiourea and prepared by one-pot ball milling at room temperature. This catalyst, in which Zn is dispersed as the single atom, displays superior activity in N-alkylation via the hydrogen-borrowing strategy (120 °C, turnover frequency (TOF) up to 8.4 h-1). S-doping significantly enhanced the catalytic activity of CNS@Zn1-AA, as it increased the specific surface area and defects of this material and simultaneously increased the electron density of Zn sites in this catalyst. Furthermore, this catalyst had excellent stability and recyclability, and no obvious loss in activity after eight runs.

Modulation of Local Charge Distribution Stabilized the Anionic Redox Process in Mn-Based P2-Type Layered Oxides.

An anionic redox reaction is an extraordinary method for obtaining high-energy-density cathode materials for sodium-ion batteries (SIBs). The commonly used inactive-element-doped strategies can effectively trigger the O redox activity in several layered cathode materials. However, the anionic redox reaction process is usually accompanied by unfavorable structural changes, large voltage hysteresis, and irreversible O2 loss, which hinders its practical application to a large extent. In the present work, we take the doping of Li elements into Mn-based oxide as an example and reveal the local charge trap around the Li dopant will severely impede O charge transfer upon cycling. To overcome this obstacle, additional Zn2+ codoping is introduced into the system. Theoretical and experimental studies show that Zn2+ doping can effectively release the charge around Li+ and homogeneously distribute it on Mn and O atoms, thus reducing the overoxidation of O and improving the stability of the structure. Furthermore, this change in the microstructure makes the phase transition more reversible. This study aimed to provide a theoretical framework for further improve the electrochemical performance of similar anionic redox systems and provide insights into the activation mechanism of the anionic redox reaction.