Modulating Electronic Structure of Iridium Single-Atom Anchored on 3D Fe-Doped ß-Ni(OH)2 Catalyst with Nanopyramid Array Structure for Enhanced Oxygen Evolution Reaction.

Developing high-performance electrocatalysts for oxygen evolution reaction (OER) is crucial in the pursuit of clean and sustainable hydrogen energy, yet still challenging. Herein, a spontaneous redox strategy is reported to achieve iridium single-atoms anchored on hierarchical nanosheet-based porous Fe doped ß-Ni(OH)2 pyramid array electrodes (SAs Ir/Fe-ß-Ni(OH)2 ), which exhibits high OER performance with a low overpotential of 175 mV at 10 mA cm-2 and a remarkable OER current density in alkaline electrolyte, surpassing Fe-ß-Ni(OH)2 /NF and IrO2 by 31 and 38 times at 1.43 V versus RHE, respectively. OER catalytic mechanism demonstrates that the conversion of * OH→* O and the active lattice O content can be significantly improved due to the modulation effect of the Ir single atoms on the local electronic structure and the redox behavior of FeNi (oxy) hydroxide true active species. This work provides a promising insight into understanding the OER enhancement mechanism for Ir single-atoms modified FeNi-hydroxide systems.

Advances in the Application of AI Robots in Critical Care: Scoping Review.

BACKGROUND: In recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. OBJECTIVE: This review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. METHODS: Following the scoping review framework proposed by Arksey and O'Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. RESULTS: Of the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. CONCLUSIONS: This review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

Coupling Ferricyanide/Ferrocyanide Redox Mediated Recycling Spent LiFePO4 with Hydrogen Production.

Replacing the oxygen evolution reaction with thermodynamically more favorable alternative oxidation reactions offers a promising alternative to reduce the energy consumption of hydrogen production. However, questions remain regarding the economic viability of alternative oxidation reactions for industrial-scale hydrogen production. Here, we propose an innovative cost-effective, environment-friendly and energy-efficient strategy for simultaneous recycling of spent LiFePO4 (LFP) batteries and hydrogen production by coupling the spent LFP-assisted ferricyanide/ferrocyanide ([Fe(CN)6 ]4- /[Fe(CN)6 ]3- ) redox reaction. The onset potential for the electrooxidation of [Fe(CN)6 ]4- to [Fe(CN)6 ]3- is low at 0.87 V. Operando Raman and UV/Visible spectroscopy confirm that the presence of LFP in the electrolyte allows for the rapid reduction of [Fe(CN)6 ]3- to [Fe(CN)6 ]4- , thereby completing the [Fe(CN)6 ]4- /[Fe(CN)6 ]3- redox cycle as well as facilitating the conversion of spent LiFePO4 into LiOH ⋅ H2 O and FePO4 . The electrolyzer consumes 3.6 kWh of electricity per cubic meter of H2 produced at 300 mA cm-2 , which is 43 % less than conventional water electrolysis. Additionally, this recycling pathway for spent LFP batteries not only minimizes chemical consumption and prevents secondary pollution but also presents significant economic benefits.

Bi-Functional Co/Al Modified 1T-MoS2 /rGO Catalyst for Enhanced Uranium Extraction and Hydrogen Evolution Reaction in Seawater.

Uranium is a key element in the preparation of nuclear fuel. An electrochemical uranium extraction technique is proposed to achieve high efficiency uranium extraction performance through HER catalyst. However, it is still a challenge to design and develop a high-performance hydrogen evolution reaction (HER) catalyst for rapid extraction and recovery of uranium from seawater. Herein, a bi-functional Co, Al modified 1T-MoS2 /reduced graphene oxide (CA-1T-MoS2 /rGO) catalyst, showing a good HER performance with a HER overpotential of 466 mV at 10 mA cm-2 in simulated seawater, is first developed. Benefiting from the high HER performance of CA-1T-MoS2 /rGO, efficient uranium extraction is achieved with a uranium extraction capacity of 1990 mg g-1 in simulated seawater without post-treatment, exhibiting a good reusability. The results of experiments and density functional theory (DFT) show that a high uranium extraction and recovery capability is attributed to the synergy effect of the improved HER performance and the strong adsorption capacity between U and OH*. This work provides a new strategy for the design and preparation of bi-functional catalysts with high HER performance and uranium extraction and recovery capabilities in seawater.

Synthesis and biological evaluation of N-(3-fluorobenzyl)-4-(1-(methyl-d3)-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-amine as a novel, potent ALK5 receptor inhibitor.

Specific inhibition of ALK5 provides a novel method for controlling the development of cancers and fibrotic diseases. In this work, a novel series of N-(3-fluorobenzyl)-4-(1-(methyl-d3)-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-amine (11), a potential clinical candidate, was synthesized by strategic incorporation of deuterium at potential metabolic soft spots and identified as ALK5 inhibitors. This compound has a low potential for CYP-mediated drug-drug interactions as a CYP450 inhibitor (IC50 = >10 µM) and showed potent inhibitory effects in cellular assay (IC50 = 3.5 ± 0.4 nM). The pharmacokinetic evaluation of 11 in mice demonstrated moderate clearance (29.0 mL/min/kg) and also revealed high oral bioavailability in mice (F = 67.6%).

Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke.

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.

Novel FeNi-Based Nanowires Network Catalyst Involving Hydrophilic Channel for Oxygen Evolution Reaction.

Developing novel, efficient, and low-cost 3D FeNi-based oxygen evolution reaction (OER) catalysts with the special hydrophilic channel is still a challenge for improving hydrogen production efficiency. Herein, a novel 3D ethoxy substituted FeNi oxalate (ENWs-FeNi-C2 O4 ) nanowires network catalyst with hydrophilic channels is reported firstly, which shows an outstanding OER activity with a low overpotential (215 mV at 10 mA cm-2 ) and small Tafel slope (54.5 mV dec-1 ). OER catalytic mechanism indicates that the OH adsorption step and O2 bubble diffusion step of OER reaction process can be significantly improved due to the special hydrophilic channels, and the ethoxy as an interlayer ligand not only expands the interlayer distance of layered FeNi (oxy) hydroxide true active species but modulates its electronic structure, promoting the *OOH formation step, and thus exhibiting the outstanding OER performance. This work provides a novel idea for the preparation of novel and efficient OER electro-catalysts with special 3D structures.

Mesenchymal stem cells regulate activation of microglia cells to improve hippocampal injury of heat stroke rats.

Heat stroke is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Mesenchymal stem cells (MSCs) are currently believed to have anti-inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on heat stroke-induced excessive inflammation and neurological dysfunction. We established a heat stroke model in rats under conditions of continuous high temperature and high humidity. After modeling, rats were randomly divided into heat stroke model group, MSCs treatment group and normal temperature control group without any treatment. We performed survival analysis, neurological deficit score, histological staining of hippocampus and cerebellum, immunofluorescence staining of microglia, detection of inflammatory and chemokine levels in the hippocampus and cerebellum in each group. We found that MSCs treatment not only significantly reduced early (day 3) and late (day 28) mortality, but also prominently reduced nerve injury in heat stroke rats, and improved pathology and neuronal cell damage in the hippocampus and cerebellum. In addition, MSCs treatment can significantly inhibit the over-activation of hippocampal microglia in heat stroke rats and the levels of pro-inflammatory factors and chemokines in the hippocampus. Early treatment of MSCs can greatly promote the activation of cerebellar microglia in heat stroke rats. Meanwhile, MSCs treatment has an inhibitory effect on the level of chemokine in the cerebellum of rats in the early stage of heat stroke. In conclusion, the application of MSCs in the treatment of heat stroke in rats can significantly reduce mortality and neurological deficits and improve hippocampal damage, possibly by inhibiting the excessive activation of hippocampal microglia in heat stroke rats.

Analysis of the short-term prognosis and risk factors of elderly acute kidney injury patients in different KDIGO diagnostic windows.

BACKGROUND AND AIMS: Follow-up observation was performed on elderly acute kidney injury (AKI) patients to analyze the short-term prognosis and risk factors of AKI patients in the 48-h diagnostic window and 7-day diagnostic window of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS: Inpatients aged ≥ 75 years in the geriatric ward of the People's Liberation Army General Hospital, China, between January 2007 and December 2015 were selected as the research subjects. According to two diagnostic criteria in the KDIGO guidelines, patients were divided into a 48-h diagnostic window group and a 7-day diagnostic window group. The medical data of the patients were divided into the death group and the survival group for analysis based on the survival condition of the patients after 90 days of AKI. Factors that affected the 90-day survival of patients in the 48-h diagnostic window and 7-day diagnostic window groups were analyzed using multivariate Cox regression. RESULTS: During the follow-up period, a total of 652 patients were enrolled in this study. Among them, 623 cases were men, accounting for 95.6% of the patients. The median age was 87 (84-91) years. According to the KDIGO staging criteria, there were 308 (47.2%) cases in AKI stage 1, 164 (25.2%) cases in stage 2, and 180 (27.6%) cases in stage 3. Among the 652 patients, 334 (51.2%) were diagnosed with AKI based on the 48-h diagnostic criteria window, and 318 (48.8%) were diagnosed with AKI based on the baseline 7-day diagnostic criteria. The 90-day mortality of AKI patients was 42.5% in the 48-h diagnostic window and 24.2% in the 7-day diagnostic window. The multivariate Cox analysis results showed that low mean arterial pressure (HR = 0.966; P < 0.001), low serum prealbumin level (HR = 0.932; P < 0.001), infection (HR = 1.448; P = 0.047), mechanical ventilation (HR = 1.485; P = 0.038), high blood urea nitrogen (BUN) level (HR = 1.026; P < 0.001), blood magnesium level (HR = 2.560; P = 0.024), and more severe AKI stage (stage 2: HR = 3.482; P < 0.001 and stage 3: HR = 6.267; P < 0.001) were independent risk factors affecting the 90-day mortality of elderly patients in the 48-h diagnostic window, whereas low body mass index (HR = 0.851; P < 0.001), low mean arterial pressure (HR = 0.980; P = 0.036), low serum prealbumin level (HR = 0.950; P = 0.048), low serum albumin level (HR = 0.936; P = 0.015), high BUN level (HR = 1.046; P < 0.001), and more severe AKI stage (stage 2: HR = 4.249; P = 0.001 and stage 3: HR = 9.230; P < 0.001) were independent risk factors affecting the 90-day mortality of elderly patients in the 7-day diagnostic window. CONCLUSIONS: The clinical differences of AKI and risk factors for 90-day mortality in elderly AKI individuals vary depending on the definition used. An increment of Scr ≥ 26.5 µmol/L in 48 h (48-h KDIGO window) alone predicts adverse clinical outcomes.

Auscultation-assisted bedside postpyloric placement of feeding tube in critically ill patients: a prospective, observational study.

BACKGROUND AND OBJECTIVES: To assess the efficacy and safety of auscultation-assisted bedside postpyloric feeding tube (ABPFT) placement in early enteral nutritional support for critically ill patients. METHODS AND STUDY DESIGN: A prospective observational study was conducted and 92 critically ill patients who met the inclusion criteria undergoing ABPFT placement after the intravenous injection of 10 mg of metoclopramide were included. Abdominal X-ray was performed to confirm the location of the catheter tip. End points investigated were the success rate of tube placement, rate of jejunal tube placement, duration of the procedure, length of insertion, and number of attempts. Operational-related adverse events or complications were also documented and evaluated. RESULTS: The total success rate of postpyloric feeding tube implantation was 97.8% (90/92), among which, 89.1% (82/92) of the tubes were placed proximal to the jejunum. The first-attempt success rate was 91.3% (84/92) and the mean attempt per individual patient was 1.11±0.38 times. The mean operation time was 28.6±17.7 minutes, and the mean insertion length of tube was 106±9.6 cm. A total of 27 adverse events occurred in 19.6% (18/92) patients and there was no serious adverse events or complications during the study period. CONCLUSIONS: Assistance by auscultation can significantly improve the success rate of nasal feeding tube placement. This simple, safe and fast approach is feasible for the application among health practitioners in the intensive care unit.

The impact of daily use of an enteral feeding checklist on clinical outcomes in shock patients: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: The optimal delivery of enteral nutrition in shock patients has an important prognostic clinical value; thus, checklists for standardizing enteral nutrition should be developed. This study examined whether the use of an enteral feeding checklist can improve enteral nutrition in shock patients. METHODS AND STUDY DESIGN: A retrospective cohort study was conducted. A multidisciplinary working group developed an enteral feeding checklist. Information on patients' demographics, checklist items, and clinical outcomes was collected. RESULTS: In total, 148 patients were included. The checklist was used for 35 patients but not for the remaining 113 patients. Patients in the checklist group received enteral nutrition earlier (2.6 vs 4.6 days, p=0.017) and had a lower mechanical ventilation rate (62.9% vs 85.0%, p=0.004). The checklist group had shorter intensive care unit stay (mean 17.3 vs 25.7 days, p=0.043). No significant differences were observed in 28- and 90- day mortality, mechanical ventilation duration, and intolerance to enteral nutrition. CONCLUSIONS: The use of an enteral feeding checklist in shock patients was associated with earlier enteral nutrition delivery and decreased intensive care unit stay.

Frictional Reduction with Partially Exfoliated Multi-Walled Carbon Nanotubes as Water-Based Lubricant Additives.

In this work, partially exfoliated multi-walled carbon nanotubes (Px-CNTs) were prepared by oxidizing multi-walled carbon nanotubes (MWCNTs) and applied into water-based lubricant as a kind of new additives, resulting in an outstanding anti-friction effect. The Px-CNTs have the structures of both MWCNTs and graphene oxide nanoribbons (GONRs). The special structure could prevent aggregation in water-based lubricant and reduce friction effectively. At the same time, Px-CNTs generate both sliding and rolling friction like MWCNTs and GONRs simultaneously. The friction force of Px-CNTs tended to go up after declining with increasing its loading, suggesting the existence of optimum additive amount of additions. Compared with water, water with 0.5 wt% Px-CNTs further reduced the friction force up to 66.4%. Compared with CNTs-COOH and GONRs dispersed in water via a similar method, Px-CNTs in water displays remarkable friction characteristic, suggesting that the friction force of water with 0.5 wt% Px-CNTs is decreased by 19.82% and 13.82% compared with water with 0.3 wt% MWCNTs and GONRs.

Inactivation of EWS reduces PGC-1α protein stability and mitochondrial homeostasis.

EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor γ Coactivator (PGC-1α), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1α via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1α and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1α expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid ß-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1α protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation.

A Smart Superwetting Surface with Responsivity in Both Surface Chemistry and Microstructure.

Recently, smart surfaces with switchable wettability have aroused much attention. However, only single surface chemistry or the microstructure can be changed on these surfaces, which significantly limits their wetting performances, controllability, and applications. A new surface with both tunable surface microstructure and chemistry was prepared by grafting poly(N-isopropylacrylamide) onto the pillar-structured shape memory polymer on which multiple wetting states from superhydrophilicity to superhydrophobicity can be reversibly and precisely controlled by synergistically regulating the surface microstructure and chemistry. Meanwhile, based on the excellent controllability, we also showed the application of the surface as a rewritable platform, and various gradient wettings can be obtained. This work presents for the first time a surface with controllability in both surface chemistry and microstructure, which starts some new ideas for the design of novel superwetting materials.

Self-Restoration of Superhydrophobicity on Shape Memory Polymer Arrays with Both Crushed Microstructure and Damaged Surface Chemistry.

Recently, self-healing superhydrophobic surfaces have become a new research focus due to their recoverable wetting performances and wide applications. However, until now, on almost all reported surfaces, only one factor (surface chemistry or microstructure) can be restored. In this paper, a new superhydrophobic surface with self-healing ability in both crushed microstructure and damaged surface chemistry is prepared by creating lotus-leaves-like microstructure on the epoxy shape memory polymer (SMP). Through a simple heating process, the crushed surface microstructure, the damaged surface chemistry, and the surface superhydrophobicity that are destroyed under the external pressure and/or O2 plasma action can be recovered, demonstrating that the obtained superhydrophobic surface has a good self-healing ability in both of the two factors that govern the surface wettability. The special self-healing ability is ascribed to the good shape memory effect of the polymer and the reorganization effect of surface molecules. This paper reports the first use of SMP material to demonstrate the self-healing ability of surface superhydrophobicity, which opens up some new perspectives in designing self-healing superhydrophobic surfaces. Given the properties of this surface, it could be used in many applications, such as self-cleaning coatings, microfluidic devices, and biodetection.

Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND: Regional citrate or heparin is often prescribed as an anticoagulant for continuous renal replacement therapy (CRRT). However, their efficacy and safety remain controversial. Therefore, we performed this meta-analysis to compare these two agents and to determine whether the currently available evidence is sufficient and conclusive by using trial sequential analysis (TSA). METHODS: We searched for relevant studies in PubMed, Embase, the Cochrane Library databases and the China National Knowledge Infrastructure (CNKI) Database from database inception until September 2015. We selected randomized controlled trials comparing regional citrate with heparin in adult patients with acute kidney injury (AKI) who were prescribed CRRT. RESULTS: Fourteen trials (n = 1134) met the inclusion criteria. Pooled analyses showed that there was no difference in mortality between the regional citrate and heparin groups (relative risk (RR) 0.97, 95 % confidence interval (CI) 0.84, 1.13, P > 0.05), which was confirmed by TSA. Compared with heparin, regional citrate significantly prolonged the circuit life span in the continuous venovenous haemofiltration (CVVH) subgroup (mean difference (MD) 8.18, 95 % CI 3.86, 12.51, P < 0.01) and pre-dilution subgroup (MD 17.51, 95 % CI 9.85, 25.17, P < 0.01) but not in the continuous venovenous haemodiafiltration (CVVHDF) subgroup (MD 28.60, 95 % CI -3.52, 60.73, P > 0.05) or post-dilution subgroup (MD 13.06, 95 % CI -2.36, 28.48, P > 0.05). However, the results were not confirmed by TSA. A reduced risk of bleeding was found in the regional citrate compared with the systemic heparin group (RR 0.31, 95 % CI 0.19, 0.51, P < 0.01) and TSA provided conclusive evidence. Fewer episodes of heparin-induced thrombocytopoenia (HIT) (RR 0.41, 95 % CI 0.19, 0.87, P = 0.02) and a greater number of episodes of hypocalcaemia (RR 3.96, 95 % CI 1.50, 10.43, P < 0.01) were found in the regional citrate group. However, TSA did not provide conclusive evidence. CONCLUSION: In adult patients with AKI, there is no difference in mortality between the regional citrate and heparin treated groups. However, regional citrate is more efficacious in prolonging circuit life span and reducing the risk of bleeding and should be recommended as the priority anticoagulant for critically ill patients who require CRRT.

Subglottic secretion suction for preventing ventilator-associated pneumonia: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Potential benefits of subglottic secretion suction for preventing ventilator-associated pneumonia (VAP) are not fully understood. METHODS: We searched Cochrane Central, PubMed, and EMBASE up to March 2016 to identify randomized controlled trials (RCTs) that compared subglottic secretion suction versus non-subglottic secretion suction in adults with mechanical ventilation. Meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0. The primary outcome was incidence of VAP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the level of evidence. RESULTS: Twenty RCTs (N = 3544) were identified. Subglottic secretion suction was associated with reduction of VAP incidence in four high quality trials (relative risk (RR) 0.54, 95 % confidence interval (CI) 0.40-0.74; p < 0.00001) and in all trials (RR = 0.55, 95 % CI 0.48- 0.63; p < 0.00001). Sensitivity analyses did not show differences in the pooled results. Additionally, the results of the above-mentioned analyses were confirmed in TSA. GRADE level was high. Subglottic secretion suction significantly reduced incidence of early onset VAP, gram-positive or gram-negative bacteria causing VAP, and duration of mechanical ventilation. It delayed the time-to-onset of VAP. However, no significant differences in late onset VAP, intensive care unit (ICU) mortality, hospital mortality, or ICU length of stay were found. CONCLUSIONS: Subglottic secretion suction decreased VAP incidence and duration of mechanical ventilation and delayed VAP onset. However, subglottic secretion suction did not reduce mortality and length of ICU stay. Subglottic secretion suction is recommended for preventing VAP and for reducing ventilation length, especially in the population at high risk of early onset VAP. TRIAL REGISTRATION: A protocol of this meta-analysis has been registered on PROSPERO (registration number: CRD42015015715 ); registered on 5 January 2015.

In vivo construction of tissue-engineered cartilage using adipose-derived stem cells and bioreactor technology.

The present study aims to investigate the feasibility of tissue-engineered cartilage constructed in vivo and in vitro by dynamically culturing adipose-derived stem cells (ADSCs) with an articular cartilage acellular matrix in a bioreactor and subsequently implanting the cartilage in nude mice. ADSCs were proliferated, combined with three dimensional scaffolds (cell density: 5 × 10(7)/mL) and subsequently placed in a bioreactor and culture plate for 3 weeks. In the in vivo study, complexes cultured for 1 week under dynamic or static states were subcutaneously implanted into nude mice and collected after 3 weeks. Indicators such as gross morphology, histochemistry and immunohistochemistry were examined. In the in vitro study, histological observation showed that most scaffolds in the dynamic group were absorbed, and cell proliferation and matrix secretion were significant. Positive staining of safranin-O and alcian blue II collagen stain in the dynamic group was significantly stronger than that in the static culture group. In the in vivo study, cartilage-like tissues formed in the specimens of the two groups. Histological examination showed that cell distribution in the dynamic group was relatively more uniform than in the static group, and matrix secretion was relatively stronger. Bioreactor culturing can promote ADSC proliferation and cartilage differentiation and is thus a suitable method for constructing tissue-engineered cartilage in vivo.

Transcriptional activation of p21(WAF¹/CIP¹) is mediated by increased DNA binding activity and increased interaction between p53 and Sp1 via phosphorylation during replicative senescence of human embryonic fibroblasts.

Although p21(WAF1/CIP1) is known to be elevated during replicative senescence of human embryonic fibroblasts (HEFs), the mechanism for p21 up-regulation has not been elucidated clearly. In order to explore the mechanism, we analyzed expression of p21 mRNA and protein and luciferase activity of full-length p21 promoter. The result demonstrated that p21 up-regulation was accomplished largely at transcription level. The promoter assay using serially-deleted p21 promoter constructs revealed that p53 binding site was the most important site and Sp1 binding sites were necessary but not sufficient for transcriptional activation of p21. In addition, p53 protein was shown to interact with Sp1 protein. The interaction was increased in aged fibroblasts and was regulated by phosphorylation of p53 and Sp1. DNA binding activity of p53 was significantly elevated in aged fibroblasts but that of Sp1 was not. DNA binding activities of p53 and Sp1 were also regulated by phosphorylation. Phosphorylation of p53 at serine-15 and of Sp1 at serines appears to be involved. Taken together, the result demonstrated that p21 transcription during replicative senescence of HEFs is up-regulated by increase in DNA binding activity and interaction between p53 and Sp1 via phosphorylation.

Immunotherapy in the context of sepsis-induced immunological dysregulation.

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.