Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling.

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

Cooperative Catalysis-Enabled (4 + 3) Cycloaddition of 2-Indolylmethanols with In Situ-Generated ortho-Naphthoquinone Methides.

A cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols with ortho-naphthoquinone methides (o-NQMs), which were in situ-generated from enynones, has been established in the presence of silver/Brønsted acid cocatalysts. In the reaction pathway, the key o-NQM intermediates were formed through Ag(I)-catalyzed cyclization of enynones, while the indole-based carbocation intermediates were generated via Brønsted acid-catalyzed dehydration of 2-indolylmethanols. By this approach, a wide range of seven-membered cyclohepta[b]indoles were synthesized in good yields with high efficiency under mild reaction conditions, which serves as a useful strategy toward constructing indole-fused seven-membered rings. Moreover, the catalytic asymmetric version of this (4 + 3) cycloaddition has been realized under the cooperative catalysis of Ag(I) with chiral phosphoric acid, which offered chiral cyclohepta[b]indole with a good enantioselectivity (75% ee). This work not only represents the first cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols but also provides a good example for o-NQM-involved cycloadditions, which will contribute to the chemistry of 2-indolylmethanols and enrich the research contents of cooperative catalysis.

Construction of Highly Accurate Machine Learning Potential Energy Surfaces for Excited-State Dynamics Simulations Based on Low-Level Data Sets.

Machine learning is capable of effectively predicting the potential energies of molecules in the presence of high-quality data sets. Its application in the construction of ground- and excited-state potential energy surfaces is attractive to accelerate nonadiabatic molecular dynamics simulations of photochemical reactions. Because of the huge computational cost of excited-state electronic structure calculations, the construction of a high-quality data set becomes a bottleneck. In the present work, we first built two data sets. One was obtained from surface hopping dynamics simulations at the semiempirical OM2/MRCI level. Another was extracted from the dynamics trajectories at the CASSCF level, which was reported previously. The ground- and excited-state potential energy surfaces of ethylene-bridged azobenzene at the CASSCF computational level were constructed based on the former low-level data set. Although non-neural network machine learning methods can achieve good or modest performance during the training process, only neural network models provide reliable predictions on the latter external test data set. The BPNN and SchNet combined with the Δ-ML scheme and the force term in the loss functions are recommended for dynamics simulations. Then, we performed excited-state dynamics simulations of the photoisomerization of ethylene-bridged azobenzene on machine learning potential energy surfaces. Compared with the lifetimes of the first excited state (S1) estimated at different computational levels, our results on the E isomer are in good agreement with the high-level estimation. However, the overestimation of the Z isomer is unimproved. It suggests that smaller errors during the training process do not necessarily translate to more accurate predictions on high-level potential energies or better performance on nonadiabatic dynamics simulations, at least in the present case.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Global Trends in Research of Programmed Cell Death in Osteoporosis: A Bibliometric and Visualized Analysis (2000-2023).

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

Comparison of Fusion Rate and Clinical Outcomes in Minimally Invasive and Conventional Posterior Fusion for Lumbar Degenerative Disease: A Network Meta-Analysis.

BACKGROUND: The fusion rate, clinical efficacy, and complications of minimally invasive fusion surgery and open fusion surgery in the treatment of lumbar degenerative disease are still unclear. METHODS: We conducted a literature search using PubMed, Embase, Cochrane Library, CNKI, and WANFANG databases. RESULTS: This study included 38 retrospective studies involving 3,097 patients. Five intervention modalities were considered: unilateral biportal endoscopic-lumbar interbody fusion (UBE-LIF), percutaneous endoscopic-lumbar interbody fusion (PE-LIF), minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF). Quality assessment indicated that each study met acceptable quality standards. PE-LIF demonstrated reduced low back pain (OR=0.50, CI: 0.38-0.65) and lower complication rate (OR=0.46, CI: 0.25-0.87) compared to PLIF. However, in indirect comparisons, PE-LIF showed the lowest fusion rates, with the ranking as follows: UBE-LIF (83.2%) > MIS-TLIF (59.6%) > TLIF (44.3%) > PLIF (39.8%) > PE-LIF (23.1%). With respect to low back pain relief, PE-LIF yielded the best results, with the order of relief as follows: PE-LIF (96.4%) > MIS-TLIF (64.8%) > UBE-LIF (62.6%) > TLIF (23.0%) > PLIF (3.2%). Global and local consistency tests showed satisfactory results, and heterogeneity tests indicated good stability. CONCLUSIONS: Compared to conventional open surgery, minimally invasive fusion surgery offered better scores for low back pain and Oswestry Disability Index, lower complication rates, reduced bleeding, and shorter hospital stays. However, minimally invasive fusion surgery did not show a significant advantage in terms of fusion rate and had a longer operative time.

The effect of oral antiviral therapy for COVID-19 in managing non-hospitalized patients with lung cancer.

BACKGROUNDS: The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer. METHODS: Utilizing data from the TriNetX - a global health research network, a retrospective cohort study was conducted involving 2484 patients diagnosed with both lung cancer and COVID-19. Propensity score matching (PSM) was employed to create well-balanced cohorts. The study assessed the primary outcome of all-cause hospitalization or mortality within a 30-day follow-up. RESULTS: After PSM, the oral antiviral group exhibited a significantly lower risk of the primary composite outcome compared to the control group (6.1 % vs. 9.9 %; HR: 0.60; 95 % CI: 0.45-0.80). This association was consistent across various subgroups according to age, sex, vaccine status, type of oral antiviral agent, and lung cancer characteristics. Additionally, the oral antiviral group showed a lower risk of all-cause hospitalization (HR: 0.73; 95 % CI: 0.54-0.99) and a significantly lower risk of mortality (HR: 0.16; 95 % CI: 0.06-0.41). CONCLUSION: The study suggests a favorable impact of oral antiviral therapy on the outcomes of COVID-19 in individuals with lung cancer and support the potential utility of oral antiviral agents in improving outcomes in this vulnerable population.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Effects of percutaneous endovascular angioplasty for severe stenosis or occlusion of subclavian artery.

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.

Complex immune microenvironment of chordoma: a road map for future treatment.

BACKGROUND: Chordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial. METHODS: We employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma. RESULTS: Previous research by van Oost et al argued that compared with other sarcomas, chordomas typically exhibit an immunologically "hot" microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of "cold" and "hot". Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells. CONCLUSIONS: These findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma.

Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Phlorizin from Lithocarpus litseifolius [Hance] Chun ameliorates FFA-induced insulin resistance by regulating AMPK/PI3K/AKT signaling pathway.

BACKGROUND: Insulin resistance (IR) is the central pathophysiological feature in the pathogenesis of metabolic syndrome, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia. As the main active ingredient in Lithocarpus litseifolius [Hance] Chun, previous studies have shown that phlorizin (PHZ) can reduce insulin resistance in the liver. However, the effect of phlorizin on attenuating hepatic insulin resistance has not been fully investigated, and whether this effect is related to AMPK remains unclear. PURPOSE: The present study aimed to further investigate the effect of phlorizin on attenuating insulin resistance and the potential action mechanism. METHODS: Free fatty acids (FFA) were used to induce insulin resistance in HepG2 cells. The effects of phlorizin and FFA on cell viability were detected by MTT analysis. Glucose consumption, glycogen synthesis, intracellular malondialdehyde (MDA), superoxide dismutase (SOD), total cholesterol (TC), and triglyceride (TG) contents were quantified after phlorizin treatment. Glucose uptake and reactive oxygen species (ROS) levels in HepG2 cells were assayed by flow cytometry. Potential targets and signaling pathways for attenuating insulin resistance by phlorizin were predicted by network pharmacological analysis. Moreover, the expression levels of proteins related to the AMPK/PI3K/AKT signaling pathway were detected by western blot. RESULTS: Insulin resistance was successfully induced in HepG2 cells by co-treatment of 1 mM sodium oleate (OA) and 0.5 mM sodium palmitate (PA) for 24 h. Treatment with phlorizin promoted glucose consumption, glucose uptake, and glycogen synthesis and inhibited gluconeogenesis in IR-HepG2 cells. In addition, phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells. Network pharmacological analysis showed that AKT1 was the active target of phlorizin, and the PI3K/AKT signaling pathway may be the potential action mechanism of phlorizin. Furthermore, western blot results showed that phlorizin ameliorated FFA-induced insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. CONCLUSION: Phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells and ameliorated hepatic insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. Our study proved that phlorizin played a role in alleviating hepatic insulin resistance by activating AMPK, which provided experimental evidence for the use of phlorizin as a potential drug to improve insulin resistance.

Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration.

OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.

Protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step immunoprecipitation approach.

Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses. For complete details on the use and execution of this protocol, please refer to Li et al.1.

[Hip joint biomechanical analysis of the acetabular anatomical reconstruction and nonanatomical reconstruction in total hip arthroplasty for Crowe type â ¢ developmental dysplasia of the hip by finite element method].

OBJECTIVE: To analyze the hip joint biomechanics of the acetabular anatomical reconstruction and nonanatomical reconstruction in total hip arthroplasty (THA) for Crowe type Ⅲ developmental dysplasia of the hip (DDH) by finite element method, which provided theoretical foundation and experimental basis for the anatomical acetabular reconstruction during THA in clinical practice. METHODS: One patient with left end-stage hip arthritis secondary to Crowe type Ⅲ DDH was selected in this study, who underwent total hip arthroplasty in the orthopedic department of the First Affiliated Hospital of Bengbu Medical College in April 2020. This patient was female, 57 years old. The preoperative and postoperative three dimentional CT scan of the patient's pelvis were performed. Fourteen acetabular cup models with different anteversion, inclination and rotation center height were established in Mimics and 3-Matic software. The boundary and load conditions were set in Abaqus software. The Von Mises and stress distribution of the hip joint were calculated and observed. RESULTS: In the Crowe type Ⅲ DDH THA, if the hip rotation center was restored anatomically and the acetabular cup's inclination was set as 40°, the cup's anteversion varied from 5° to 25°, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 20°anteversioin;if the hip rotation center was restored anatomically and the acetabular cup's anteversion was set as 15°, the cup's inclination varied from 35° to 55°, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 35° inclination;if the acetabular cup's anteversion and inclination were set as 15°and 40°respectively, the up migration of hip rotaion center varied from 0 mm to 20 mm, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 10 mm up migration. In all fourteen models, the Von Mises value of the acetabulum, acetabulum cup and polyethylene liner were lowest when the acetabular cup's anteversion and inlcination were 15°, 35° respectively, as well as the rotation center was restored anatomically. CONCLUSION: In total hip arthroplasty for Crowe type Ⅲ DDH, the anatomical restoration of hip rotation center with 15° anteversion and 35° inclination of the acetabular cup are suggested, bone graft above the acetabular cup and additional screws are recommended simultaneously to further reduce the Von Mises of hip joint.

Ultrahigh Heat/Fire-Resistant, Mechanically Robust, and Closed-Loop Chemical Recyclable Polycarbonate Enabled by Facile Bond Dissociation Energy Modulation.

Plastics serve as an essential foundation in contemporary society. Nevertheless, meeting the rigorous performance demands in advanced applications and addressing their end-of-life disposal are two critical challenges that persist. Here, an innovative and facile method is introduced for the design and scalable production of polycarbonate, a key engineering plastic, simultaneously achieving high performance and closed-loop chemical recyclability. The bisphenol framework of polycarbonate is strategically adjusted from the low-bond-dissociation-energy bisphenol A to high-bond-dissociation-energy 4,4'-dihydroxydiphenyl, in combination with the incorporation of polysiloxane segments. As expected, the enhanced bond dissociation energy endows the polycarbonate with an extremely high glow-wire flammability index surpassing 1025 °C, a 0.8 mm UL-94 V-0 rating, a high LOI value of 39.2%, and more than 50% reduction of heat and smoke release. Furthermore, the π-π stacking interactions within biphenyl structures resulted in a significant enhancement of mechanical strength by as more as 37.7%, and also played a positive role in achieving a lower dielectric constant. Significantly, the copolymer exhibited outstanding closed-loop chemical recyclability, allowing for facile depolymerization into bisphenol monomers and the repolymerized copolymer retains its high heat and fire resistance. This work provides a novel insight in the design of high-performance and closed-loop chemical recyclable polymeric materials.