Comprehensive Comparison of Three Different Medicinal Parts of Eupatorium lindleyanum DC. Using the RRLC-Q-TOF-MS-Based Metabolic Profile and In Vitro Anti-Inflammatory Activity.

Eupatorium lindleyanum DC. (EL) is a traditional Chinese herb known for its phlegm-reducing, cough-relieving and asthma-calming properties. It is widely used for treating cough and bronchitis. However, preliminary experiments have revealed wide variations in the composition of its different medicinal parts (flowers, leaves and stems), and the composition and efficacy of its different medicinal parts remain largely underexplored at present. In this study, non-targeted rapid resolution liquid chromatography coupled with a quadruple time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics approach was developed to investigate the differences in the chemical composition of different medicinal parts of EL. We identified or tentatively identified 9 alkaloids, 11 flavonoids, 14 sesquiterpene lactones, 3 diterpenoids and 24 phenolic acids. In addition, heatmap visualization, quantitative analysis by high-performance liquid chromatography (HPLC-PDA) and ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) showed particularly high levels of sesquiterpene lactones, flavonoids and phenolic acids in the flowers, such as eupalinolide A and B and chlorogenic acid, among others. The leaves also contained some flavonoid sesquiterpene lactones and phenolic acids, while the stems were almost absent. The findings of in vitro activity studies indicated that the flowers exhibited a notable inhibitory effect on the release of the inflammatory factors TNF-α and IL-6, surpassing the anti-inflammatory efficacy observed in the leaves. Conversely, the stems demonstrated negligible anti-inflammatory activity. The variations in anti-inflammatory activity among the flowers, leaves and stems of EL can primarily be attributed to the presence of flavonoids, phenolic acids and sesquiterpene lactones in both the flowers and leaves. Additionally, the flowers contain a higher concentration of these active components compared to the leaves. These compounds mediate their anti-inflammatory effects through distinct biochemical pathways. The results of this study are anticipated to provide a scientific basis for the rational and effective utilization of EL resources.

Risk factors for in-hospital mortality in recipients of allogeneic hematopoietic stem cell transplantation with acute respiratory distress syndrome: a retrospective study based on the 2023 new definition of acute respiratory distress syndrome.

INTRODUCTION: ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. METHODS: From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. RESULTS: Under the new definition, SOFA score (OR = 1.351, 95% CI: 1.146-1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972-0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164-3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961-0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313-40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072-1.265, P < 0.01) were independently associated with in-hospital mortality. CONCLUSION: These prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.

Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aß) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aß plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aß plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.

Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the Identification of Immune-Related Targets in Esophageal Squamous Cell Carcinoma.

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.

Risk and Pathological Factors of Recurrence after Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The risk and pathological factors of recurrence after endoscopic resection (ER) for superficial esophageal squamous cell carcinoma (ESCC) are inconsistent across studies. We evaluated this in a systematic review and meta-analysis. METHODS: The data of recurrence in such patients was extracted from all studies. Risk ratios (RRs) were combined using random-effects meta-analysis, to assess pooled recurrence rate and pathological risk factors. Relapse-free survival was combined using the Kaplan-Meier method to estimate the relationship between various pathological factors and recurrence time. RESULTS: We identified 26 studies, with a total of 5100 patients and 321 with recurrences (pooled rate, 6.2%). The risk of recurrence was significantly higher in positive vertical margin (VM) (RR [95% CI]: 4.51 [2.16 - 9.44]), positive horizontal margin (HM) (RR [95% CI]: 2.54 [1.57 - 4.13]), lymphovascular invasion (LVI) (RR [95% CI]: 2.33 [1.75 - 3.11], P < 0.001), lymphatic invasion (LI) (RR [95% CI]: 2.24 [1.24 - 4.06]), and tumor invading submucosa ≤200 µm (SM1) (RR [95% CI]: 1.71 [1.32 - 2.21], compared to muscularis mucosa). Patients with LI (HR 2.47; 95% CI 1.24 - 4.90; P = 0.02) and LVI (HR 2.36; 95% CI 2.22 - 4.59; P = 0.0006) tended to have earlier recurrence after ER. CONCLUSION: The recurrence rate of superficial ESCC after ER is acceptable. Patients with positive margins, LVI, LI and SM1 need to pay significant attention to the risk of recurrence. LI and VI should be evaluate separately. (PROSPERO CRD42023406309).

Development of esophagogastroduodenoscopy in China: results from the national census in 2013 and 2020.

Background: Given the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period. Methods: Two national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources. Results: From 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P<0.001), more tertiary hospitals performing EGD per million inhabitants (OR 2.43, P<0.001), higher incidence of esophageal and gastric cancer (OR 2.09, P=0 016), and higher number of hospitals performing EGD per million inhabitants (OR 1.77, P=0.01) tended to provided more numerous and qualitied EGD. And hospital grading, regional GDP, incidence of esophageal and gastric cancer and the volume of EGD were observed as the significantly relevant factors of malignant dictation rate (MDR) (P<0.05), but not the number and educational background of endoscopists. Conclusion: Over the past seven years, China has made significant progress in EGD. However, challenges persist in terms of quality and inequality.

CKIP-1-Loaded Cartilage-Affinitive Nanoliposomes Reverse Osteoarthritis by Restoring Chondrocyte Homeostasis.

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-ß (TGF-ß) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.

Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Enhancing the Biological Performance of Titanium Alloy through In Situ Modulation of the Surface Nanostructure: Near-Infrared-Responsive Antibacterial Function and Osteoinductivity.

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.

Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

The effect of emotion regulation strategies on nomophobia in college students: The masking role of resilience.

College students have a high prevalence of nomophobia. However, research on the effects of emotion regulation and resilience on nomophobia in China is lacking. This research investigated how cognitive reappraisal and expressive suppression strategies directly and indirectly affect nomophobia through resilience. Therefore, from March to May 2023, 756 university student volunteers (21.4 % men) were selected from a university in northeastern China for a questionnaire survey. Our findings suggest that college students' resilience has a masking effect on the relationship between cognitive reappraisal and nomophobia and can attenuate the negative effect of the frequency of using cognitive reappraisal strategies on nomophobia. The frequency of expressive suppression strategies directly and positively affected nomophobia. Early psychological interventions targeting resilience might be potentially effective in alleviating nomophobia among college students.

Rapid evaluation of the quality of Smilax glabra Roxb. using QADS based on FT-NIR combined with multiple intelligent algorithms.

Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties. Herein, this study collected the proportion of SGR adulteration and used high-performance liquid chromatography (HPLC) to measure the astilbin content of SGR. Then Fourier-transform near-infrared (FT-NIR) technology, combined with multivariate intelligent algorithms, was used to establish partial least squares regression quantitative models for detecting SGR adulteration and measuring astilbin content, respectively. The method conducted a quantitative analysis of dual indicators through single-spectrum data acquisition (QADS) to comprehensively evaluate the authenticity and superiority of SGR. The coefficients of determination (R2) for both the calibration and prediction sets exceeded 0.96, which successfully leverages FT-NIR combined with multivariate intelligent algorithms to considerably enhance the accuracy and reliability of quantitative models. Overall, this research holds substantial value in the comprehensive quality evaluation in functional health foods.

Extracellular Vesicles Derived from Neutrophils Accelerate Bone Regeneration by Promoting Osteogenic Differentiation of BMSCs.

The reconstruction of bone defects has been associated with severe challenges worldwide. Nowadays, bone marrow mesenchymal stem cell (BMSC)-based cell sheets have rendered this approach a promising way to facilitate osteogenic regeneration in vivo. Extracellular vesicles (EVs) play an essential role in intercellular communication and execution of various biological functions and are often employed as an ideal natural endogenous nanomedicine for restoring the structure and functions of damaged tissues. The perception of polymorphonuclear leukocytes (neutrophils, PMNs) as indiscriminate killer cells is gradually changing, with new evidence suggesting a role for these cells in tissue repair and regeneration, particularly in the context of bone healing. However, the role of EVs derived from PMNs (PMN-EVs) in bone regeneration remains largely unknown, with limited research being conducted on this aspect. In the current study, we investigated the effects of PMN-EVs on BMSCs and the underlying molecular mechanisms as well as the potential application of PMN-EVs in bone regeneration. Toward this end, BMSC-based cell sheets with integrated PMN-EVs (BS@PMN-EVs) were developed for bone defect regeneration. PMN-EVs were found to significantly enhance the proliferation and osteogenic differentiation of BMSCs in vitro. Furthermore, BS@PMN-EVs were found to significantly accelerate bone regeneration in vivo by enhancing the maturation of the newly formed bone in rat calvarial defects; this is likely attributable to the effect of PMN-EVs in promoting the expression of key osteogenic proteins such as SOD2 and GJA1 in BMSCs. In conclusion, our findings demonstrate the crucial role of PMN-EVs in promoting the osteogenic differentiation of BMSCs during bone regeneration. Furthermore, this study proposes a novel strategy for enhancing bone repair and regeneration via the integration of PMN-EVs with BMSC-based cell sheets.

An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering.

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.

Distribution of pathogens and risk factors for post-replantation wound infection in patients with traumatic major limb mutilation.

PURPOSE: Even though replantation of limb mutilation is increasing, postoperative wound infection can result in increasing the financial and psychological burden of patients. Here, we sought to explore the distribution of pathogens and identify risk factors for postoperative wound infection to help early identification and managements of high-risk patients. METHODS: Adult inpatients with severed traumatic major limb mutilation who underwent replantation from Suzhou Ruixing Medical Group between November 09, 2014, and September 6, 2022 were included in this retrospective study. Demographic, and clinical characteristics, treatments, and outcomes were collected. Data were used to analyze risk factors for postoperative wound infection. RESULTS: Among the 249 patients, 185 (74.3%) were males, the median age was 47.0 years old. Postoperative wound infection in 74 (29.7%) patients, of whom 51 (20.5%) had infection with multi-drug resistant bacteria. Ischemia time (OR 1.31, 95% CI 1.13-1.53, P = 0.001), wound contamination (OR 6.01, 95% CI 2.38-15.19, P <0.001), and stress hyperglycemia (OR 23.37, 95% CI 2.30-236.93, P = 0.008) were independent risk factors, while the albumin level after surgery (OR 0.94, 95% CI 0.89-0.99, P = 0.031) was significant associated with the decrease of postoperative wound infection. Ischemia time (OR 1.21, 95% CI 1.05-1.40, P = 0.010), wound contamination (OR 8.63, 95% CI 2.91-25.57, P <0.001), and MESS (OR 1.32, 95% CI 1.02-1.71, P = 0.037 were independent risk factors for multi-drug resistant bacteria infection. CONCLUSIONS: Post-replantation wound infection was common in patients with severe traumatic major limb mutilation, and most were multi-drug resistant bacteria. Ischemia time and wound contamination were associated with the increase of postoperative wound infection, including caused by multi-drug resistant. Positive correction of hypoproteinemia and control of stress hyperglycemia may be beneficial.

Cryo-EM structure of cytochrome bo3 quinol oxidase assembled in peptidiscs reveals an "open" conformation for potential ubiquinone-8 release.

Cytochrome bo3 quinol oxidase belongs to the heme­copper-oxidoreductase (HCO) superfamily, which is part of the respiratory chain and essential for cell survival. While the reaction mechanism of cyt bo3 has been studied extensively over the last decades, specific details about its substrate binding and product release have remained unelucidated due to the lack of structural information. Here, we report a 2.8 Å cryo-electron microscopy structure of cyt bo3 from Escherichia coli assembled in peptidiscs. Our structural model shows a conformation for amino acids 1-41 of subunit I different from all previously published structures while the remaining parts of this enzyme are similar. Our new conformation shows a "U-shape" assembly in contrast to the transmembrane helix, named "TM0", in other reported structural models. However, TM0 blocks ubiquinone-8 (reaction product) release, suggesting that other cyt bo3 conformations should exist. Our structural model presents experimental evidence for an "open" conformation to facilitate substrate/product exchange. This work helps further understand the reaction cycle of this oxidase, which could be a benefit for potential drug/antibiotic design for health science.

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome.

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.

Association between physical activity and risk of gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: Lifestyle plays an important role in preventing and managing gastroesophageal reflux disease (GERD). In response to the conflicting results in previous studies, we performed a systematic review and meta-analysis to investigate this association. METHODS: Relevant studies published until January 2023 were retrieved from 6 databases, and the prevalence of symptomatic gastroesophageal reflux (GER) or GERD was determined from the original studies. A random effects model was employed to meta-analyze the association by computing the pooled relative risk (RR) with 95% confidence intervals (95%CIs). Furthermore, subgroup and dose-response analyses were performed to explore subgroup differences and the association between cumulative physical activity (PA) time and GERD. RESULTS: This meta-analysis included 33 studies comprising 242,850 participants. A significant negative association was observed between PA and the prevalence of symptomatic GER (RR = 0.74, 95%CI: 0.66-0.83; p < 0.01) or GERD (RR = 0.80, 95%CI: 0.76-0.84; p < 0.01), suggesting that engaging in PA might confer a protective benefit against GERD. Subgroup analyses consistently indicated the presence of this association across nearly all subgroups, particularly among the older individuals (RR<40 years:RR≥40 years = 0.85:0.69, p < 0.01) and smokers (RRsmoker:RRnon-smoker = 0.67:0.82, p = 0.03). Furthermore, a dose-response analysis revealed that individuals who engaged in 150 min of PA per week had a 72.09% lower risk of developing GERD. CONCLUSION: Maintaining high levels of PA decreased the risk of GERD, particularly among older adults and smokers. Meeting the recommended PA level of 150 min per week may significantly decrease the prevalence of GERD.

Influence of thermal maturity on carbazole distributions in coal source rocks during compaction pyrolysis experiments.

Carbazole compounds are widely used in determining the direction of petroleum migration, but the effect of thermal maturity on carbazoles is still ambiguity. In this paper, using compaction pyrolysis simulation experiments, artificial mature samples with vitrinite reflectance (Ro) range from 0.38 to 3.0% were acquired. And the content and composition change characteristics of carbazole compounds were analyzed in coal source rocks. The experimental results showed that thermal maturity controls the generation of a large amount of carbazole compounds in coal rocks. Compared with the low mature stage, the content of carbazole compounds was about 10-100 times higher in the mature stage. With the increasing maturity, in the coal sample, the content of carbazole compounds showed a trend of first increasing and then decreasing. In derivatives of carbazole, the corresponding maturity for the maximum generation of ethylcarbazole (EC), dimethylcarbazole (DMCA), methylcarbazole (MCA), carbazole (CA) and benzocarbazole (BCA) performed the increasing sequence. With the increasing maturity, the relative abundance of 2-MCA, 1,7-DMCA and benzo[a]carbazole increased with the increasing maturity, while 4-MCA, 1,4-DMCA and benzo[c]carbazole gradually decreased. Benzocarbazole ratio [a]/[a] +[ c] varies only in a narrow range 0.36-0.61 in the entire maturity range, suggesting limited maturity dependence. The experimental conclusion provides more theoretical basis for future geochemical analysis using carbazole compounds.

Self-similarity study based on the particle sizes of coal-series diatomite.

Coal-series diatomite (CSD) is widely distributed in China and has poor functional and structural properties and exhibits limited utilization of high value-added materials, resulting in a serious waste of resources and tremendous pressure on the environment. Moreover, due to differences in the mineralogical characteristics of CSD, different particle size scales (PSSs) have different functional structures and exhibit different self-similarities. In this study, we took CSD as the research object and PSS as the entry point and carried out a self-similarity study based on gas adsorption and an image processing method to illustrate the microstructures and self-similarities of different PSSs. The results showed that the pore structure of the CSD was dominated by mesopores and macropores and basically lacked micropores. The fractal dimensions were calculated with the Frenkel-Haisey-Hill (FHH) model and Menger model, and the DF1 values for - 0.025 mm and - 2 mm were 2.51 and 2.48, respectively, and the DM1 values were 3.75 and 3.79, respectively, indicating that the mesopore structure of the fine PSS was complex, whereas macropores were present in the coarse PSS. MATLAB was programmed to obtain grayscale thresholds, binarized images, grayscale histograms, three-dimensional (3D) reconstruction images and box dimensions, which enabled us to observe the microstructures and self-similarities of the CSD. Self-similarity studies based on particle sizes are very important for functional application of CSD.Please note that article title mismatch between MS and JS we have followed MS, kindly check and cofirm.Yes, I have checked and confirmed.Kindly check and confirm corresponding author mail id are correctly identified.Yes, I have checked and confirmed.