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Abstract Background The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. Methods Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. Results 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. Conclusions The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.

Abstract Background Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. Methods In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. Results The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. Conclusions The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.

Abstract Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

ABSTRACT: In ruminants, IFN-tau (IFNT) regulates the production of prostaglandins (PG) in the endometrium, which is crucial for conceptus adhesion. However, the related molecular regulatory mechanisms remain unclear. Forkhead box O1 (FOXO1), a member of the FOXO subfamily of transcription factors, is known to be important for mouse implantation and decidualization. In this study, we determined the spatiotemporal expression profile of FOXO1 in goat endometrium during early pregnancy. FOXO1 was highly expressed in the glandular epithelium since the onset of conceptus adhesion (d 16 of pregnancy). Then, we validated that FOXO1 could bind to the promoter of prostaglandin-endoperoxide synthase 2 (PTGS2) and increase its transcription. And the expression profile of PTGS2 was similar to that of FOXO1 in the peri-implantation uterus. Moreover, IFNT could upregulate the levels of FOXO1 and PTGS2 in goat uterus and primary endometrial epithelium cells (EEC). In EEC, the intracellular content of PGF2α was positively correlated with the levels of IFNT and FOXO1. Altogether, we found an IFNT/FOXO1/PTGS2 axis that controls the synthesis of PGF2α but not prostaglandin E2 in goat uterine glands. These findings contribute to better understanding the function of FOXO1 in the reproductive physiology of goats and provide more insights into the implantation of small ruminants.

Abstract Objectives Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+ plasma cells subset (PCs) in LN. Methods C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin–eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+ PC subsets in the blood and kidneys of mice were determined by flow cytometry. Results In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1β and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression. Conclusion This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.

With the advancement of scientific research, an increasing number of studies on metal nanozymes, particularly Au NPs, have been conducted. They possess glucose oxidase (GOD)-like activity and peroxidase (POD)-like activity, with GOD-like activity receiving the most attention. However, there is a lack of research and summary on future trends in Au NPs in biomedical field. Therefore, we conducted a study on the GOD-like activity of Au NPs based on 158 relevant publications downloaded from the Web of Science Core Collection between 2007 and 2023, using citation metrics, authors, nations, institutions, cited references, and keywords. We found that Au NPs were initially utilized for glucose biosensors, glucose detection in human serum, and the detection of other carbohydrates and proteins. Researchers have recently focused on its application in oncotherapy and diabetic wound treatment. In addition to being utilized to treat autoimmune illnesses, inflammation, and other diseases, Au NPs may eventually replace insulin and antibiotics. We anticipate that the use of Au NPs will increase in the future. We hope this study will serve as a guide for future researchers so that Au NPs can be applied more broadly and competently.

Abstract Background The fixation of inferior pole fractures of the patella (IPFPs) is still a great challenge for surgeons. Materials and methods We introduced a new fixation method for IPFP fixation, that is, separate vertical wiring plus bilateral anchor girdle suturing fixation (SVW-BSAG). Three finite element models including the anterior tension band wiring (ATBW) model, separate vertical wiring (SVW) model and SVW-BSAG model, were built to evaluate the fixation strength of different fixation methods. A total of 41 consecutive patients with IPFP injury were enrolled in this retrospective study, including 23 patients in the ATBW group and 18 patients in the SVW-BSAG group. The operation time, radiation exposure, full weight-bearing time, Bostman score, extension lag versus contralateral healthy leg, Insall–Salvati ratio, and radiograph outcomes were employed to assess and compare the ATBW group and SVW-BSAG group. Results The finite element analysis confirmed that the SVW-BSAG fixation method was as reliable as the ATBW fixation method in terms of fixed strength. Through retrospective analysis, we found that there was no significant difference between the SVW-BSAG and ATBW groups in age, sex, BMI, fracture side, fracture type, or follow-up time. There were no significant differences between the two groups in the Insall–Salvati ratio, 6-month Bostman score, and fixation failure. Compared with the ATBW group, the SVW-BSAG group showed advantages in intraoperative radiation exposure, full weight-bearing time, and extension lag versus the contralateral healthy leg. Conclusion The finite element analysis and clinical results showed that SVW-BSAG fixation methods are a reliable and valuable for IPFP treatment.

Abstract Objective Excessive postoperative sliding is a common complication of intramedullary nails in the treatment of intertrochanteric femur fractures. The aim of this study was to identify risk factors for excessive postoperative sliding in the intertrochanteric fractures treated with an intramedullary nail. Methods A retrospective analysis of 369 patients with femoral intertrochanteric fractures treated with short intramedullary nails between February 2017 and September 2020 was performed. Patients were classified into an excessive sliding group (ES group) and a control group according to the sliding distance after 6 months of follow-up. The proximal medullary filling degree (MFD), fracture reduction patterns in the anteroposterior (AP) view and lateral view, and tip-apex distance (TAD) were evaluated and compared in each group. Results Thirty-three cases were included in the ES group, and 336 cases were included in the control group. No significant differences in age, sex, fracture side, AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification, Dorr classification, Singh Osteoporosis Index (SOI), American Society of Anesthesiologists classification (ASA), TAD or fracture reduction patterns in the AP view were noted between the two groups. The negative reduction pattern can strongly predict excessive postoperative sliding (OR 4.286, 95% CI 1.637–11.216, P = 0.003). The incidence of excessive postoperative sliding increased by 8.713-fold when the MFD decreased by 10% (OR 8.713, 95% CI 1.925–39.437, P = 0.005). Conclusions A low medullary filling degree and negative fracture reduction pattern in the lateral view were both independent risk factors for excessive postoperative sliding.

Lung cancer is one of the most common malignant tumors with poor prognosis and its incidence and mortality are maintained at a high level in China. In recent years with the development of next-generation sequencing, the studies on the correlation between microbiome and lung cancer and biomarkers have increased for providing references to early diagnosis and clinical treatment of lung cancer; some of the studies have indicated that lung cancer patients′ microbiome of various body parts differ significantly from those of the healthy people and the changes in microbiome due to other respiratory diseases could affect the occurrence and development of lung cancer. In the paper, the studies on the relation between microbiome and lung cancer are reviewed; shortcomings of previous researches and prospects of future studies are also discussed.

Abstract We appreciate the interest by Drs. Hagiyama and coauthors in our work entitled “Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures”. They discussed several pertinent points and it is our pleasure to respond their concerns in order. Firstly, we agree that calcar fracture gap and anteromedial cortical support are different concepts, though both of them were used to evaluate the displacement of fracture reduction quality. Secondly, our primary outcome parameter was the threshold distance of calcar fracture gapping in anteroposterior and lateral fluoroscopies, which was calculated based on sensitivity and specificity by receiver operating characteristic curves. Thirdly, we took immediate post-operative fluoroscopic images in 3 views to describe the initial reduction quality as baseline to compare and calculate the changes with three-dimensional computed tomography, which was taken about one week after operation for confirming secondary stability after head-neck sliding and impaction. Lastly, the parameters selected in multivariable analysis. Future work with better study-design is needed to improve the prediction of patient outcomes.

Abstract Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

In 2020, the Chinese government proposed the goals of “peaking carbon dioxide emissions” in 2030 and reaching “carbon neutrality” in 2060, with the expectation of enhancing the optimization of industrial structure and energy structures as well as promoting the development of control technologies and new energy technologies for pollution prevention. Carbon emissions lead to global warming, glacier melting, sea level rising, and other unexpected climate changes. It is highly significant to develop sustainable technologies for treating or converting carbon dioxide and low value-added solid carbon wastes and other carbon pollutants to achieve solid-state valuable carbon products. Carbon pollutants are also regarded as secondary carbon resources, which provide sufficient raw materials for developing carbon materials. Graphitization alters the chemical structure of carbonaceous materials. However, there are still some critical issues in the traditional graphitization processes, such as high processing temperature, insufficient graphitization, and emission of greenhouse gas. In recent years, an efficient and environmentally friendly method for electrochemical graphitization in molten salts has been established, which can be used to directly convert carbon pollutants into high graphitized products. In this review, there are three main topics: (1) process flow, (2) structure characteristics, (3) conversion mechanism of electrochemical graphitization. The use of carbon nanomaterials in secondary batteries such as lithium-ion batteries and aluminum-ion batteries has been discussed for a potential application. As a result, the efficient strategies of transforming and utilizing abundant secondary carbon resources to achieve the applications have also been analyzed. Finally, the ultimate goals for bridging the gap between molten salt electrochemical graphitization and engineering of graphitized products have been identified. Further efforts should be made to develop large-scale electrolytic technology with low energy consumption, build advanced in-situ characterization technology and quantitative analysis method for high-temperature molten salt electrochemistry, and understand the mechanism of electrochemical graphitization at the microscale.

ObjectiveThe inverted triangle configuration of the three cannulated screws is the classic fixation method most commonly performed for undisplaced femoral neck fractures in young and geriatric patients. However, the posterosuperior screw has a high incidence of cortical breach, known as an in-out-in (IOI) screw. In this study, we present a novel posterosuperior screw placement strategy to prevent the screw from becoming IOI.MethodsUsing computed tomography data and image-processing software, 91 undisplaced femoral neck fractures were reconstructed. The anteroposterior (AP), lateral, and axial radiographs were simulated. To simulate the intraoperative screw placement process, participants used three screw insertion angles (0°, 10°, and 20°) to place the screw on the AP and lateral views of the radiograph according to the three established strategies. On the AP radiograph, a screw was placed abutting (strategy 1), 3.25 mm away from (strategy 2), or 6.5 mm away from (strategy 3) the superior border of the femoral neck. On the lateral radiograph, all the screws were placed abutting the posterior border of the femoral neck. Axial radiographs were used to evaluate the screw position.ResultsIn strategy 1, all the placed screws were IOI regardless of the screw insertion angle. In strategy 2, 48.3% (44/91) of IOI screws occurred at a 0° screw insertion angle, 41.7% (38/91) of IOI screws occurred at a 10° screw insertion angle, and 42.9% (39/91) of IOI screws occurred at a 20° screw insertion angle situation. In strategy 3, no IOI screw occurred, and the screw insertion angles did not affect the safety and accuracy of screw placement.ConclusionsScrews placed according to strategy 3 are safe. The reliability of this screw placement strategy is unaffected by a screw insertion angle of less than 20 degrees.

Abstract We employed MC‐ICP‐MS to measure the mass‐dependent Ca isotope compositions of Vesta‐related meteorites. Eucrites and diogenites show distinct Ca isotope compositions, which is caused by crystallization of isotopically heavy orthopyroxene. The Ca isotope data support a model where the two lithologies are linked, where the diogenites, mainly composed of orthopyroxene crystallized from an eucritic melt. As normal eucrites are the main Ca reservoir on Vesta, their δ44/40Ca values (per mil 44Ca/40Ca ratios relative to NIST 915a) best represents that of bulk silicate Vesta (0.83 ± 0.04‰). This value is different from those of bulk Earth (0.94 ± 0.05‰) and Mars (1.04 ± 0.07‰), suggesting that there exists notable Ca isotope heterogeneity between inner solar system bodies. The δ44/40Ca difference between chondrules and these planets does not support the pebble accretion model as the main mechanism for planetary growth.

Psychological stress emerges to be a common health burden in the current society for its highly related risk of mental and physical disease outcomes. However, how the quickly-adaptive stress response process connects to the long-observed organismal alterations still remains unclear. Here, we investigated the profile of circulatory extracellular vesicles (EVs) after acute stress (AS) of restraint mice by phenotypic and proteomic analyses. We surprisingly discovered that AS-EVs demonstrated significant changes in size distribution and plasma concentration compared to control group (CN) EVs. AS-EVs were further characterized by various differentially expressed proteins (DEPs) closely associated with biological, metabolic and immune regulations and were functionally important in potentially underlying multiple diseases. Notably, we first identified the lipid raft protein Stomatin as an essential biomarker expressed on the surface of AS-EVs. These findings collectively reveal that EVs are a significant function-related liquid biopsy indicator that mediate circulation alterations impinged by psychological stress, while also supporting the idea that psychological stress-associated EV-stomatin can be used as a biomarker for potentially predicting acute stress responses and monitoring psychological status. Our study will pave an avenue for implementing routine plasma EV-based theranostics in the clinic.

Hermetic pressurized buildings have been developed to reduce the effects of high altitude. The behavior and effect of fire in this new type of building have not been studied before. Unlike common buildings, the inside pressure in this new type of building is maintained at around standard atmospheric pressure, which is significantly higher than the outside environment pressure in high altitude regions. In addition, at the early stage of a fire, the oxygen required to maintain combustion in the sealed building is supplied by mechanical vents (if in operation) instead of opening windows or doors as in common buildings. This paper presents a case study on the behavior of fire in a sealed pressurized hotel building located in Tibet. Fire dynamics simulator (FDS) is used to study fire behavior under different design fire scenarios. Available evacuation time under different fire scenarios are obtained by analyzing oxygen concentration, gas content, temperature, visibility and other indicators. Based on this, a fire protection design scheme is suggested.

This article focuses on the interaction between China's industrial agglomeration, foreign direct investment (FDI) and environmental pollution of public health in the past 15 years. By conducting theoretical and empirical research, we try to reveal the relationship and mechanism between the economic growth and public health from the perspective of environmental pollution. By constructing an embedded theoretical model of industrial agglomeration and FDI, this article combines other environmental pollution influencing factors, expounds the impact mechanism of industrial agglomeration on environmental pollution. Based on the provincial-level panel data of China on environmental pollution and industrial agglomeration, the empirical test is carried out through the threshold panel regression model. According to the results, industrial agglomeration can significantly rectify the regional environmental pollution, thereby benefiting public health. FDI has a phased impact on the relationship between industrial agglomeration and environmental pollution. Specifically, when the level of FDI is low, the positive improvement effect of industrial agglomeration on environmental pollution is relatively strong. This is mainly because industrial agglomeration can promote economic growth, technological progress, and enhance environmental awareness. When the level of FDI exceeds the first threshold and continues to rise, the positive improvement effect of industrial agglomeration is maximized. Before the level of FDI exceeds the second threshold, this effect gradually weakens. The population concentration and excessive expansion of city scale brought about by industrial agglomeration will lead to the increase of regional resource and energy consumption, thus aggravating environmental pollution. The policy implication is that while the government and enterprises are vigorously increasing the level of foreign investment, they must pay equal attention to economic growth and public health, and the level of industrial agglomeration should match the level of foreign investment so as to give full play to the positive improvement effect of industrial agglomeration on environmental pollution, and realize the coordinated development of the regional economy, environment and population health.

Functional nanoprobes which detect specific food hazards quickly and simply are still in high demand in the field of food-safety inspection research. In the present work, a dual-emission metal-organic framework-based ratiometric fluorescence probe was integrated to detect Cu2+ and Pb2+ with rapidness and ease. Specifically, quantum dots (QDs) and carbon quantum dots (CQDs) were successfully embedded into zeolitic imidazolate framework-67 (ZIF-67) to function as a novel ratiometric fluorescent sensing composite. The ratiometric fluorescence signal of CQDs/QDs@ZIF-67 was significantly aligned with the concentration of metal ions to give an extremely low detection limit of 0.3324 nM. The highly sensitive and selective CQDs/QDs@ZIF-67 composite showed potential for the rapid and cost-effective detection of two metal ions.

This study aimed to compare ozone-microbubble-washing (OM) performed by domestic equipment with conventional water-washing (CW) regarding resultant quality attributes of muscle foods. For this purpose, muscle microstructure and lipid and protein oxidation were evaluated in pork and fish samples after OM and CW treatments. The assessment of muscle microstructure showed that OM treatment did not damage the microstructure of muscle fibers in both pork and fish samples. Thiobarbituric acid reactive substances (TBARS) values were not detected in both treatment groups, and they were substantially below the generally acceptable threshold (1 mg MDA/kg). The methylglyoxal (MGO) level of OM-treated fish samples was significantly higher than that of CW-treated fish samples. However, glyoxal (GO) and MGO levels of OM-treated pork samples were significantly lower than that of CW-treated pork samples. Similar types and sites of oxidative modification and similar numbers of modified peptides, as well as no significant difference in the concentration of total and most of the free amino acids (FAA) between treatment groups, indicated that OM treatment did not accelerate protein oxidation.

Abstract Background Dysregulation of eukaryotic translation elongation factor 1 delta (EEF1D) in cancers has been reported; however, the role and mechanisms of EEF1D in osteosarcoma remain poorly understood. The aim of this study is to investigate the expression and role of EEF1D in osteosarcoma and to elucidate its underlying mechanisms. Methods The expression of EEF1D in osteosarcomas and cell lines was evaluated by qRT-PCR, Western blotting and immunohistochemistry. EEF1D knockdown using small interfering RNA (siRNA) was employed to analyze the role of EEF1D in osteosarcoma cell proliferation and cell cycle progression. The host signaling pathways affected by EEF1D knockdown were detected using PathScan® intracellular signaling array kit. Results The expression of EEF1D was found to be up-regulated in human osteosarcoma tissues and cell lines. Its expression was positively correlated with Enneking stage and the tumor recurrence. EEF1D knockdown inhibited osteosarcoma cell proliferation, colony-forming ability, and cell cycle G2/M transition in vitro. In addition, EEF1D knockdown decreased the levels of phospho-Akt, phospho-mTOR, and phospho-Bad proteins. Conclusions EEF1D is upregulated in osteosarcoma and plays a tumor promoting role by facilitating Akt-mTOR and Akt-Bad signaling pathways. Accordingly, EEF1D is a potential target for cancer therapy.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-1 and IFN-1-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/-mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-1, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-1-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases. [ABSTRACT FROM AUTHOR]

During conventional intermittent intraoperative neuromonitoring (IONM) in thyroidectomy, recurrent laryngeal nerve (RLN) injury is detected by an electromyographic (EMG) loss of signal (LOS) after the nerve dissection. Exclusive continuous monitoring during the phase of RLN dissection may be helpful in detecting adverse EMG changes earlier. A total of 208 RLNs at risk were enrolled in this study. Standardized IONM procedures were followed. We continuously stimulated the RLN at the lower exposed end with a stimulator to exclusively monitor the real-time quantitative EMG change during RLN dissection. Once the amplitude decreased by more than 50% of the initial signal, the surgical maneuver was paused and the RLN was retested every minute for 10 minutes to determine amplitude recovery before restarting the dissection. The procedure was feasible in all patients. No LOS was encountered in this study. Nineteen RLNs had an amplitude reduction of more than 50%. Eighteen nerves showed gradual amplitude recovery (16 nerves had a traction injury and two nerves had a compression injury). After 10 minutes, the recovery was complete (i.e., >90%) in eight nerves, 70–90% in seven nerves, and 50–70% in three nerves. Among these 18 nerves, only one nerve developed temporary vocal palsy because it was exposed to unavoidable repeated nerve traction after restarting the dissection. Another nerve showed no gradual recovery from thermal injury, and developed temporary vocal palsy. The temporary and permanent palsy rates were 1% and 0%, respectively. During intermittent IONM, exclusive real-time monitoring of the RLN during dissection is an effective procedure to detect an adverse EMG change, and prevent severe RLN injuries that cause LOS.