Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1ß and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Single-Crystal Perovskite for Solar Cell Applications.

The advent of organic-inorganic hybrid metal halide perovskites has revolutionized photovoltaics, with polycrystalline thin films reaching over 26% efficiency and single-crystal perovskite solar cells (IC-PSCs) demonstrating ≈24%. However, research on single-crystal perovskites remains limited, leaving a crucial gap in optimizing solar energy conversion. Unlike polycrystalline films, which suffer from high defect densities and instability, single-crystal perovskites offer minimal defects, extended carrier lifetimes, and longer diffusion lengths, making them ideal for high-performance optoelectronics and essential for understanding perovskite material behavior. This review explores the advancements and potential of IC-PSCs, focusing on their superior efficiency, stability, and role in overcoming the limitations of polycrystalline counterparts. It covers device architecture, material composition, preparation methodologies, and recent breakthroughs, emphasizing the importance of further research to propel IC-PSCs toward commercial viability and future dominance in photovoltaic technology.

Construction of sensitive quality indicators for rapid rehabilitation care of patients after combined pancreaticoduodenectomy.

AIM: To construct evidence-based sensitive quality indicators for patients' rapid rehabilitation care after combined pancreaticoduodenectomy (PD) and to provide a reference for clinical nursing professionals to scientifically evaluate the quality of patients' rehabilitation post-PD. BACKGROUND: Since PD is associated with higher surgical risk and anastomotic complications, it leads to higher complication rates and longer postoperative recovery cycles. This reiterates the need for rapid recovery of patients after PD; however, the evaluation of sensitive nursing care indicators regarding rapid recovery post-PD has not yet been established to date. METHODS: Based on the Donabedian structure-process-result theory model, we used available literature, semi-structured interviews, the Delphi method, and hierarchical analysis to establish a sensitive indicator system for patients' rapid rehabilitation after PD and evaluate the importance of such indicators. RESULTS: There were two rounds of expert correspondence, and the effective recovery rate of the questionnaires of these rounds was 100%. The expert authority coefficients, as well as the Kendall coordination coefficients of the expert opinions, were 0.859 and 0.872 as well as 0.423 and 0.431, with statistically significant differences (p < 0.05), respectively. Consequently, we developed a sensitive quality index system for patients' rapid rehabilitation care after combined PD, including 3 first-level, 12 s-level, and 23 third-level indexes, respectively. CONCLUSION: The constructed sensitive quality index system developed for patients' rapid rehabilitation nursing care after combined PD is standardized, practical, and aligned with the specialty characteristics. Furthermore, this might help greatly in improving the quality and safety of patients' rapid rehabilitation nursing care after combined PD, standardizing nursing management skills, and enhancing nursing quality.

Genome-wide association study of image-based trait reveals the genetic architecture of dark-induced leaf senescence in rice.

Darkness is often used as an effective measure to induce leaf senescence. Although many senescence-related genes in rice have been reported, the genome-wide genetic architecture underlying leaf senescence remains poorly understood. In our study, indica and japonica rice showed contrasting responses to dark-induced leaf senescence (DILS). Genome-wide association studies (GWAS) combined with transcriptomic analyses revealed 57, 97, and 48 loci involved in the regulation of the onset, progression, and ending of DILS, respectively. Haplotype analyses showed that the senescence-related loci differentially accumulated in indica and japonica accessions and functioned additively to regulate DILS. A total of 357 candidate genes were identified that are involved in various senescence-related processes such as lipid and amino acid catabolism, photosynthesis, response to reactive oxygen species, and regulation of defense response. In addition, functional analyses of the two candidate genes, OsMYB21 and OsSUB1B, revealed that OsMYB21 positively regulates the onset of DILS, while OsSUB1B negatively regulates its progression. Thus, our results provide new insights into the genetic regulation of DILS in rice.

Deashing Strategy on Biomass Carbon for Achieving High-Performance Full-Supercapacitor Electrodes.

The porous carbon materials, namely, MC700/800, PC700/800, and SC700/800, have been prepared using several biomasses (mushroom dreg, Chinese parasol leaves, and Siraitia grosvenorii leaves) as individual precursors at 700 and 800 °C activation temperatures. Among these carbon-negative electrodes, SC700 exhibits an impressive specific capacitance, nearly 2-fold that of commercial activated carbon (169.5 F g-1). When assembled with a Ni(OH)2 positive electrode in asymmetric supercapacitors, the SC700//Ni(OH)2 device can achieve a specific capacitance of 80 F g-1 and an energy density of 32.16 Wh kg-1 at 1700 W kg-1. In contrast, the MC700 electrode can display inferior performance potentially attributed to the high ash content in the biomass. To further optimize the activated process of the MC700 product, three deashing carbon negative electrodes (denoted as MC(H2O), MC(HF), and MC(Mix)) were prepared by deashing treatment using H2O, HF, and mixed acid, and then a modified composite positive electrode (MC700@MnO2(MCM)) has been prepared by doping with MnO2. Electrochemical testing demonstrates that the deashing strategy achieves a significant capacitance enhancement compared to the primary carbon material while maintaining excellent cyclic stability. The asymmetric supercapacitors, assembled from these decorated electrode materials, exhibited a maximum energy density of 21.08 Wh kg-1 and a power density of 1150 W kg-1 under a high-voltage window of 2.2 V. Additionally, this type of full device can power 28 LEDs for approximately 5 min.

Unlocking Lattice Oxygen on Selenide-Derived NiCoOOH for Amine Electrooxidation and Efficient Hydrogen Production.

In pursuit of advancing the electrooxidation of amines, which is typically encumbered by the inertness of C(sp3)-H/N(sp3)-H bonds, our study introduces a high-performance electrocatalyst that significantly enhances the production efficiency of vital chemicals and fuels. We propose a novel electrocatalytic strategy employing a uniquely designed (NixCo1-x)Se2-R electrocatalyst, which is activated through Se-O exchange and electron orbital spin manipulation. This catalyst efficiently generates M4+ species, thus enabling the activation of lattice oxygen and streamlining the electrooxidation of amines. Empirical evidence from isotope labeling, molecular probes, and computational analyses indicates that the electrocatalyst fosters the formation of energetically favorable peroxy radical intermediates, which substantially expedite the reaction kinetics. The refined electrocatalyst achieves an exceptional current density of 20 mA cm-2 at a potential of 1.315 V, with selectivity surpassing 99% for propionitrile, while demonstrating remarkable stability over 560 h. This work emphasizes the criticality of deciphering the fundamental mechanisms of amine electrooxidation and charts a more sustainable pathway for the nitrile and hydrogen production, marking a substantial advancement in the field of electrocatalysis.

Nitrogen-Doped Carbon Materials for Persulfate Activation via Electron Transfer Pathways.

The incorporation of nitrogen into carbon materials is a strategy that effectively boosts their catalytic potency. Herein, a nitrogen-enriched carbon substance, designated as CN0.6, was synthesized from melamine, serving as a precursor. This substance has been established to act as an efficient catalyst devoid of metals for the activation of peroxymonosulfate (PMS). At a temperature of 25 °C, a concentration of 0.05 g/L CN0.6 along with 1 mM PMS suffices to achieve the complete degradation of concentrated tetracycline hydrochloride (TC) in a short period of 4 min. This enhanced catalytic performance is attributed to the optimal level of nitrogen doping, which elevates the pyrrolic nitrogen content and introduces additional defects characterized by an ID/IG ratio of 1.02. These factors collectively augment the adsorptive capacity for PMS and create a greater number of active sites to facilitate its activation. The dominance of a nonradical electron transfer mechanism in the CN0.6/PMS system has been confirmed through a series of analyses, including radical identification, quenching tests, and electrochemical assessments. Employing high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS), the investigation identified three potential degradation routes for TC. Furthermore, the intermediates produced are determined to possess reduced toxicity in comparison to TC. The findings of this study offer a approach to the synthesis of highly efficient nitrogen-doped, metal-free catalysts, presenting a promising strategy for the degradation of environmental pollutants.

Posttraumatic stress disorder symptoms in mothers and adolescents after the Wenchuan earthquake: A cross-sectional and longitudinal network analysis.

OBJECTIVE: This study used network analysis to investigate the cross-sectional and longitudinal network between PTSD symptoms within mother-adolescent dyads at 12 and 18 months after the 2008 Wenchuan earthquake. METHODS: The sample was from the Wenchuan Earthquake Adolescent Health Cohort. 399 mother-adolescent dyads completed the Posttraumatic Stress Disorder Self-Rating Scale at 12 and 18 months after the earthquake. We assessed central symptoms (those with the most significant influence on other symptoms) and bridge symptoms (symptoms connecting different communities) in contemporary networks (i.e., cross-sectional networks). Subsequently, cross-lagged panel network analyses (CLPN) were performed to estimate longitudinal relationships among symptoms between dyads. RESULTS: In the contemporary networks, symptoms such as "intrusive thoughts" of both dyads and "flashbacks" of adolescents were central, indicating that they are crucial in maintaining the network of PTSD symptoms. Additional symptoms such as maternal "difficulty in concentration" and dyads' "pessimism and disappointment" should also be considered because of their central roles. Moreover, the temporary network did not directly replicate the contemporary networks, with adolescents' "nightmares" at 12 months having a high influence on other PTSD symptoms at 18 months. LIMITATIONS: Self-reported tools other than clinical diagnoses were used to collect data. CONCLUSIONS: These symptom-level associations at cross-sectional and longitudinal networks extend our understanding of PTSD symptoms among mother-adolescent dyads by pointing to specific key symptoms of PTSD that may drive the co-occurrence of PTSD among dyads. Recognizing these symptoms is imperative for the development of targeted interventions and treatments aimed at addressing comorbid PTSD in mother-adolescent dyads.

Preparing the developing world for the next pandemic: Evidence from China's R&D blueprint for emerging infectious diseases.

BACKGROUND: With double pressures of endemic and imported emerging infectious diseases (EIDs), China's ability to detect, prevent and control the unknown virus is of regional and global interest. This study aimed to establish an R&D Blueprint for EIDs in China by identifying the list of prioritized diseases and medical countermeasures (MCMs) that need proactive actions for the next pandemic. METHODS: The process mainly referred to the World Health Organization's prioritization methodology, supplemented by pipeline landscape, rapid risk assessment and multi-dimensional analysis. The study included five steps: 1) identifying potential pathogens, 2) screening into the long list, 3) prioritizing the long list, 4) identifying the final list and 5) generating an R&D Blueprint. RESULTS: China's R&D Blueprint identified 14 viral pathogens and two virus groups (i.e., Influenza HxNy and Coronavirus X) for proactive and representative MCM development. At least one diagnostic candidate in preclinical study, and one therapeutic and one vaccine candidate in Phase I/II clinical trials for each prioritized pathogen were suggested to be developed as strategic national stockpiles. Various generalized and innovative platform technologies were also highlighted for enhancing overall capacities of EID preparedness and response, covering basic research, experiment, detection, prevention and control, surveillance and information sharing. CONCLUSIONS: This is the first study in developing countries that established an R&D Blueprint of prioritized diseases, countermeasures and technologies. Our findings could help to drive pre-emptive scientific and technological actions toward emerging pathogens that may cause the next epidemic and could provide evidence-based strategies for developing countries to establish their national health research agenda tailored to health and research context under resource-limited settings.

Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes.

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

Neuroblastoma with high ASPM reveals pronounced heterogeneity and poor prognosis.

OBJECTIVE: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). METHODS: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. RESULTS: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348-41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. CONCLUSION: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

Gold-Catalyzed Alkyne Oxidative Cyclization/Mannich-Type Addition Cascade Reaction of Ynamides with 1,3,5-Triazinanes.

Herein, a gold-catalyzed alkyne oxidative cyclization/Mannich-type addition cascade reaction of ynamides with 1,3,5-triazinanes in the presence of a Brønsted acid has been presented. A class of functionalized fluorenes bearing a quaternary carbon center was synthesized directly with moderate to excellent yields via in situ formed α-oxo carbenes using quinoline N-oxide as the oxidant under mild reaction conditions.

Asymmetric α-Allylation of Amino Acid Esters with Alkynes Enabled by Chiral Aldehyde/Palladium Combined Catalysis.

A highly efficient, atom-economical α-allylation reaction of NH2-unprotected amino acid esters and alkynes is achieved by chiral aldehyde/palladium combined catalysis. A diverse range of α,α-disubstituted nonproteinogenic α-amino acid esters are produced in 31-92% yields and 84-97% ee values. The allylation products are utilized for the synthesis of drug molecule BMS561392 and other chiral molecules possessing complex structures. Mechanistic investigations reveal that this reaction proceeds via a chiral aldehyde-/palladium-mediated triple cascade catalytic cycle.

Inhibiting endothelial cell Mst1 attenuates acute lung injury in mice.

Lung endothelium plays a pivotal role in the orchestration of inflammatory responses to acute pulmonary insults. Mammalian sterile 20-like kinase 1 (Mst1) is a serine/threonine kinase that has been shown to play an important role in the regulation of apoptosis, stress responses, and organ growth. This study investigated the role of Mst1 in lung endothelial activation and acute lung injury (ALI). We found that Mst1 was significantly activated in inflamed lung endothelial cells (ECs) and mouse lung tissues. Overexpression of Mst1 promoted nuclear factor κ-B (NF-κB) activation through promoting JNK and p38 activation in lung ECs. Inhibition of Mst1 by either its dominant negative form (DN-Mst1) or its pharmacological inhibitor markedly attenuated cytokine-induced expression of cytokines, chemokines, and adhesion molecules in lung ECs. Importantly, in a mouse model of lipopolysaccharide-induced (LPS-induced) ALI, both deletion of Mst1 in lung endothelium and treatment of WT mice with a pharmacological Mst1 inhibitor significantly protected mice from LPS-induced ALI. Together, our findings identified Mst1 kinase as a key regulator in controlling lung EC activation and suggest that therapeutic strategies aimed at inhibiting Mst1 activation might be effective in the prevention and treatment of inflammatory lung diseases.

Safety, effectiveness and the optimal duration of preoperative imatinib in locally advanced gastric gastrointestinal stromal tumors: A retrospective cohort study.

BACKGROUND: The optimal duration of preoperative imatinib (IM) remains controversial. This study aimed to evaluate the safety, therapeutic effectiveness, and optimal duration of preoperative IM in patients with locally advanced gastric gastrointestinal stromal tumors (GIST). METHODS: The clinicopathologic data of 41 patients with locally advanced gastric GIST who received preoperative IM and underwent surgical resection from January 2014 and December 2021 were retrospectively analyzed. RESULTS: After a median of 7.0 (IQR: 4.5-10) months of preoperative IM treatment, 30 patients experienced adverse events (AEs), 80% of which were grade 1/2 AEs. The mean tumor size decreased from 12.71 ± 5.34 cm to 8.26 ± 4.00 cm, with a reduction rate of 35%. Setting 8 months as the cut-off value according to the results of ROC analysis. The proportion of laparoscopic surgery was higher in patients with short-term (≤8 months) versus long-term (>8 months) preoperative IM. Compared with the subtotal/total gastrectomy group, patients in the local gastrectomy group exhibited less intraoperative blood loss, shorter length of postoperative hospital stay, and fewer postoperative complications. The 3-year recurrence-free survival (RFS) and overall survival (OS) rates were 82.9% and 97.6%, and the expected 5-year RFS and OS rates were 75.6% and 90.2% respectively. RFS was better in the short-term than in the long-term preoperative IM treatment group, and it was also better in pre- plus postoperative IM treatment group than that in the preoperative IM alone group. Both univariate and multivariate COX analysis showed that a higher mitotic index and long-term preoperative IM treatment were associated with worse RFS, while postoperative IM treatment could significantly improve RFS. CONCLUSIONS: The study suggests that in patients with locally advanced gastric GIST, preoperative short-term (≤8 months) use of IM is associated with higher RFS than long-term use.

Clinical manifestations, treatment and prognosis of juvenile idiopathic arthritis with pulmonary involvement in China: a single centre study.

OBJECTIVES: In recent years, the distinct clinical presentations and elevated mortality rates of various subtypes of juvenile idiopathic arthritis (JIA) with pulmonary involvement have garnered significant attention. This study aimed to elucidate the clinical characteristics of pulmonary involvement in patients with JIA to improve clinicians' knowledge. METHODS: This single-centre retrospective study analysed the baseline data, treatment options, follow-up of sixty patients of JIA with pulmonary involvement in China. Patients with interstitial lung disease (ILD) were further classified in accordance with the 2013 American Thoracic Society/European Respiratory Society International multidisciplinary consensus on idiopathic interstitial pneumonia. RESULTS: Sixty patients (5.03%) with JIA were complicated with pulmonary involvement. The highest subtype was systemic JIA (sJIA, 63.3%), followed by rheumatoid factor (RF)-positive polyarthritis (pJIA, 25.0%). The incidence of macrophage activation syndrome (MAS) was 21.6%. The most common diagnosis was ILD (90%). Respiratory symptoms/signs were initially experienced by 61.7% of the patients, and respiratory support was required by 21.7%. High-resolution CT classification of sJIA revealed non-specific interstitial pneumonia (NSIP) and organising pneumonia. High-resolution CT classification of pJIA was NSIP and usually interstitial pneumonia (UIP). Patients were treated with NSAIDs, along with glucocorticoids, DMARDs, and biological agents. The survival rates after 1 and 5 years were approximately 93.3% and 90.0%, respectively. CONCLUSIONS: Patients with JIA with pulmonary involvement present with early onset, high mortality rate. JIA patients should undergo physical examination thoroughly and high-resolution CT scans, lung function tests for evaluating and monitoring the occurrence and development of pulmonary involvement in early stages to improve prognosis.

The impact of protein delivery on short-term and long-term clinical outcomes in critically ill patients: Protocol for a multicenter, prospective, observational study (The ACTION study).

BACKGROUND AND AIMS: Nutrition therapy is a vital part of the management of critically ill patients. Efforts have been made to optimize nutrition therapy in the ICU setting, and it is argued that protein might be the most important substrate to deliver during critical illness. However, the impact of protein delivery on patient-centered outcomes, including short-term and long-term outcomes, is controversial. Moreover, previous studies showed that compliance with the guidelines is poor in practice, and the amounts of protein intake vary significantly among different hospitals. The objective of this study is to describe the current practice of protein delivery for critically ill patients and to investigate the association between different protein delivery amounts and approaches during ICU admission and multiple patient-centered outcomes (short-term and long-term). METHODS: This is a multicenter, prospective, observational study conducted in 70 hospitals, aiming to recruit more than 1800 newly admitted critically ill patients who are expected to stay in ICU for at least 48 h. Data, including the baseline characteristics, illness severity scores, requirements of organ support therapy, and daily nutritional therapy, will be recorded until day 28 after enrollment unless discharge from the ICU or death occurs first. The key long-term clinical outcomes, like readmission post the index discharge and health-related quality of life, will be collected via telephone contact on Day 90 and Day 180 after recruitment. Quality of life will be assessed by the EuroQol five dimensions five-level questionnaire (EQ5D5L) visual analogue scale score. Apart from descriptive data, multivariate analyses adjusted for potential confounders will be applied to assess the association between protein intake during ICU stay and short-term and long-term clinical outcomes. ETHICS AND TRIAL REGISTRATION: This study was reviewed and approved by the ethics committee of Jinling Hospital (2021NZKY-027-01) and the participating sites. The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200067016) before enrollment.

Assessment of thermal power plant CO2 emissions quantification performance and uncertainty of measurements by ground-based remote sensing.

Thermal power plants serve as significant CO2 sources, and accurate monitoring of their emissions is crucial for improving the precision of global carbon emission estimates. In this study, a measurement method based on measuring point source plumes was employed in ground-based remote sensing experiments at the thermal power plant. By simulating CO2 plumes, we analyzed the impact of surrounding urban structures, the geometric relationship between measurement points and plumes, and the influence on measurement points selection. We also assessed the capability and uncertainties in quantifying CO2 emissions. For the Hefei power plant, CO2 emission estimates were on average 7.98 ± 10.01 kg/s higher with surface buildings compared to scenarios without buildings (approximately 4.09% error). By selectively filtering discrete data, the emission estimation errors were significantly reduced by 7.31 ± 7.13 kg/s compared to pre-filtered data. Regarding the relationship between observation paths and plume geometry, simulation studies indicated that the ability to estimate CO2 emissions varied for near and middle segment observations. The lowest emission rate error was found in the mid-segment near 1.5-2.0 km, reaching 7.13 ± 5.39 kg/s. CO2 distribution at the mid-segment position becomes more uniform relative to the near segment, making it more suitable for meeting emission estimation requirements. Optimizing measurement schemes by considering environmental factors and precisely selecting measurement points significantly enhances emission estimation accuracy, providing crucial technical support for top-down estimates of anthropogenic CO2 emissions.

Differential analysis of ubiquitin-proteomics in skeletal muscle of Duroc pigs and Tibetan fragrant pigs.

Understanding the differences in ubiquitination-modified proteins between Duroc pigs and Tibetan fragrant pigs is crucial for comprehending the growth and development of their skeletal muscles. In this study, skeletal muscle samples from 30-day-old Duroc pigs and Tibetan fragrant pigs were collected. Using ubiquitination 4D-Label free quantitative proteomics, we analyzed and identified ubiquitination-modified peptides, screening out 109 differentially expressed ubiquitination-modified peptides. Further enrichment analysis was conducted on the proteins associated with these differential peptides. GO analysis results indicated that the differential genes were primarily enriched in processes such as regulation of protein transport, motor activity, myosin complex, and actin cytoskeleton. KEGG pathway analysis revealed significant enrichment in pathways such as Glycolysis/Gluconeogenesis and Hippo signaling pathway. The differentially expressed key ubiquitinated proteins, including MYL1, MYH3, TNNC2, TNNI1, MYLPF, MYH1, MYH7, TNNT2, TTN, and TNNC1, were further identified. Our analysis demonstrates that these genes play significant roles in skeletal muscle protein synthesis and degradation, providing new insights into the molecular mechanisms of muscle development in Duroc pigs and Tibetan fragrant pigs, and offering theoretical support for breeding improvements in the swine industry.