The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

High-Efficiency Ultraviolet Electroluminescence from Multi-Resonance Phosphine Oxide Polycyclic Aromatics.

Efficient ultraviolet (UV) electroluminescent materials remain a great challenge, since short peak wavelength <400 nm and narrow full width at half maximum (FWHM) <50 nm are simultaneously required. In this sense, multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters featuring narrow-band emissions hold the promise for UV applications. Herein, a novel MR-TADF skeleton featuring carbazole-phosphine oxide (P=O) fused aromatics is developed to construct the first two UV MR emitters named CzP2PO and tBCzP2PO. In addition to synergistic resonance effects of P=O and N atom, sp3 -hybrid P atom renders the curved polycyclic planes of CzP2PO and tBCzP2PO, giving rise to their narrowband UV emissions with peak wavelengths <390 nm and FWHM<35 nm. Besides configuration quasi-planarization for radiation enhancement and quenching suppression, P=O moiety further enhances singlet-triplet coupling to facilitate reverse intersystem crossing, resulting in the state-of-the-art photoluminescence quantum yield of 62 % in tBCzP2PO doped films. As consequence, tBCzP2PO endowed its UV organic light-emitting diodes with the peak at 382 nm and FWHM of 32 nm, and especially the record-high external quantum efficiency (EQE) of 15.1 % among all kinds of UV devices. Our results demonstrate great potential of P=O based MR emitters in practical applications including optoelectronics, biology and medicine science.

Environmental exposure disparities in ultrafine particles and PM2.5 by urbanicity and socio-demographics in New York state, 2013-2020.

BACKGROUND: The spatiotemporal and demographic disparities in exposure to ultrafine particles (UFP; number concentrations of particulate matter (PM) with diameter ≤0.1 µm), a key subcomponent of fine aerosols (PM2.5; mass concentrations of PM ≤ 2.5 µm), have not been well studied. OBJECTIVE: To quantify and compare the aerosol pollutant exposure disparities for UFP and PM2.5 by socio-demographic factors in New York State (NYS). METHODS: Ambient atmospheric UFP and PM2.5 were quantified using a global three-dimensional model of chemical transport with state-of-the-science aerosol microphysical processes validated extensively with observations. We matched these to U.S. census demographic data for varied spatial scales (state, county, county subdivision) and derived population-weighted aerosol exposure estimates. Aerosol exposure disparities for each demographic and socioeconomic (SES) indicator, with a focus on race-ethnicity and income, were quantified for the period 2013-2020. RESULTS: The average NYS resident was exposed to 4451 #·cm-3 UFP and 7.87 µg·m-3 PM2.5 in 2013-2020, but minority race-ethnicity groups were invariably exposed to greater daily aerosol pollution (UFP: +75.0% & PM2.5: +16.2%). UFP has increased since 2017 and is temporally and seasonally out-of-phase with PM2.5. Race-ethnicity exposure disparities for PM2.5 have declined over time; by -6% from 2013 to 2017 and plateaued thereafter despite its decreasing concentrations. In contrast, these disparities have increased (+12.5-13.5%) for UFP. The aerosol pollution exposure disparities were the highest for low-income minorities and were more amplified for UFP than PM2.5. DISCUSSION: We identified large disparities in aerosol pollution exposure by urbanization level and socio-demographics in NYS residents. Jurisdictions with higher proportions of race-ethnicity minorities, low-income residents, and greater urbanization were disproportionately exposed to higher concentrations of UFP and PM2.5 than other NYS residents. These race-ethnicity exposure disparities were much larger, more disproportionate, and unabating over time for UFP compared to PM2.5 across various income strata and levels of urbanicity.

Machine learning algorithm can provide assistance for the diagnosis of non-ST-segment elevation myocardial infarction.

INTRODUCTION: Our aim was to use the constructed machine learning (ML) models as auxiliary diagnostic tools to improve the diagnostic accuracy of non-ST-elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: A total of 2878 patients were included in this retrospective study, including 1409 patients with NSTEMI and 1469 patients with unstable angina pectoris. The clinical and biochemical characteristics of the patients were used to construct the initial attribute set. SelectKBest algorithm was used to determine the most important features. A feature engineering method was applied to create new features correlated strongly to train ML models and obtain promising results. Based on the experimental dataset, the ML models of extreme gradient boosting, support vector machine, random forest, naïve Bayesian, gradient boosting machines and logistic regression were constructed. Each model was verified by test set data, and the diagnostic performance of each model was comprehensively evaluated. RESULTS: The six ML models based on the training set all play an auxiliary role in the diagnosis of NSTEMI. Although all models taken for comparison performed differences, the extreme gradient boosting ML model performed the best in terms of accuracy rate (0.95±0.014), precision rate (0.94±0.011), recall rate (0.98±0.003) and F-1 score (0.96±0.007) in NSTEMI. CONCLUSIONS: The ML model constructed based on clinical data can be used as an auxiliary tool to improve the accuracy of NSTEMI diagnosis. According to our comprehensive evaluation, the performance of the extreme gradient boosting model was the best.

A Survey on Autism Care, Diagnosis, and Intervention Based on Mobile Apps Focusing on Usability and Software Design.

This article presents a systematic review on autism care, diagnosis, and intervention based on mobile apps running on smartphones and tablets. Here, the term "intervention" means a carefully planned set of activities with the objective of improving autism symptoms. We guide our review on related studies using five research questions. First, who benefits the most from these mobile apps? Second, what are the primary purposes of these mobile apps? Third, what mechanisms have been incorporated in these mobiles apps to improve usability? Fourth, what guidelines have been used in the design and implementation of these mobile apps? Fifth, what theories and frameworks have been used as the foundation for these mobile apps to ensure the intervention effectiveness? As can be seen from these research questions, we focus on the usability and software development of the mobile apps. Informed by the findings of these research questions, we propose a taxonomy for the mobile apps and their users. The mobile apps can be categorized into autism support apps, educational apps, teacher training apps, parental support apps, and data collection apps. The individuals with autism spectrum disorder (ASD) are the primary users of the first two categories of apps. Teachers of children with ASD are the primary users of the teacher training apps. Parents are the primary users of the parental support apps, while individuals with ASD are usually the primary users of the data collection apps and clinicians and autism researchers are the beneficiaries. Gamification, virtual reality, and autism-specific mechanisms have been used to improve the usability of the apps. User-centered design is the most popular approach for mobile app development. Augmentative and alternative communication, video modeling, and various behavior change practices have been used as the theoretical foundation for intervention efficacy.

[Risk Factors and Prognosis of Delirium After Liver Transplantation].

Objective: To analyze the incidence, the onset time, and the risk factors of delirium after liver transplantation (LT). Methods: The clinical data of 211 patients who underwent LT at Third Xiangya Hospital, Central South University between January 2019 and December 2021 were collected to investigate the incidence and the onset time of postoperative delirium. Univariate analysis and multivariate logistic regression analysis were conducted to analyze the risk factors of delirium and to analyze the effect of delirium on clinical outcomes. Results: The incidence of delirium was 20.4% (43/211) and the median interval between LT and the onset of delirium was 19 hours. Univariate analysis showed that the preoperative Model for End-Stage Liver Disease (MELD) score≥22, preoperative length-of-stay≥7, liver cancer, preoperative hepatic encephalopathy, infections within 2 months before LT, preoperative lymphocyte value<0.5×10 9 L －1, massive amount of intraoperative red blood cell infusion, and carbapenem antibiotics use for 3 days or longer were associated with postoperative delirium. Multivariate logistic regression analysis showed that preoperative infections within 2 months before LT (odds ratio [ OR]=2.597, 95% confidence interval [ CI]: 1.135-5.944, P=0.024), preoperative MELD score≥22 ( OR=2.967, 95% CI: 1.104-7.975, P=0.031), and preoperative hepatic encephalopathy ( OR=4.700, 95% CI: 2.043-10.602, P<0.001) were independent risk factors for delirium after LT, while carbapenems antibiotics use for 3 days or longer ( OR=0.192, 95% CI: 0.083-0.441, P<0.001) was a protective factor for postoperative delirium among LT recipients. Regarding clinical outcomes, patients with delirium had longer postoperative ICU length-of-stays than those without delirium did ( P=0.025). Conclusion: There is a high incidence of postoperative delirium among patients who undergo LT and the onset time of delirium after LT is early. Risk factors include preoperative infections, high MELD score, and hepatic encephalopathy. On the other hand, the use of carbapenems can help prevent delirium.

Insulin alleviates LPS-induced ARDS via inhibiting CUL4B-mediated proteasomal degradation and restoring expression level of Na,K-ATPase α1 subunit through elevating HCF-1.

Acute respiratory distress syndrome (ARDS) is a critical disease with a high mortality rate, characterized by obstinate hypoxemia caused by accumulation of alveolar fluid and excessive uncontrolled inflammation. Na,K-ATPase α1 (ATP1A1) subunit is an important component of Na,K-ATPase that transports Na+ and K+ and scavenges alveolar fluid. The function of Na,K-ATPase is always impaired during ARDS and results in more severe symptoms of ARDS. However, the regulatory mechanism of Na,K-ATPase after ARDS remains unclear. Here, we revealed ATP1A1 was downregulated post-transcriptionally by an E3 ligase component CUL4B mediated proteasomal degradation. Moreover, we found insulin could inhibit the upregulation of CUL4B in an insulin receptor cofactor HCF-1-dependent manner. Our study resolved the molecular mechanism underlying the clearance impairment of alveolar fluid and provided a clue for the usage of insulin as a potential therapeutic medicine for ARDS.

Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. METHODS: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. RESULTS: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). CONCLUSIONS: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function.

Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of handelin.

Long-Term Outcome of a "Mother-Child" Coaxial Dual-Catheter Technique for Percutaneous Transluminal Angioplasty of Central Vein Stenosis or Occlusion in Hemodialysis Patients.

PURPOSE: This study aims to evaluate the long-term outcome and prognostic factors of a "mother-child" coaxial dual-catheter technique for percutaneous transluminal angioplasty (PTA) in the treatment of central vein stenosis (CVS) or central vein occlusion (CVO). MATERIALS AND METHODS: During September 2017 to August 2020, totally, 76 hemodialysis patients with symptomatic CVS or CVO were treated with PTA using the mother-child technique. The success rate, complications, and follow-up information were collected. Cox proportional hazard analysis was used to explore the predicting factors of primary patency. Primary patency rates of different subgroups were generated with the Kaplan-Meier analysis and compared using the log-rank (Mantel-Cox) test. RESULTS: There were 31 CVS patients and 45 CVO patients who presented with 114 PTAs. The initial procedure success rate was 98.25%. By the end of the follow-up, 57 patients (75%) had maintained functioning fistula after initial or repeated PTAs. The primary patency rates were 88.75% at 3 months, 73.36% at 6 months, 55.83% at 12 months, and 50.75% at 18 months. The secondary patency rates were 97.14% at 6 months, 87.66% at 12 months, and 82.18% at 24 months. The predictors for primary patency were history diabetes mellitus (hazard ratio [HR] = 3.1, 95% confidence interval [CI]: 1.31-7.30, P = .010), abnormal white blood cell count (HR = 1.44, 95% CI: 1.18-1.75, P < .001), lesion at subclavian-innominate vein (HR=2.75, 95% CI: 1.34-5.63, P = .006), and occlusion (HR=0.33, 95% CI: 0.14-0.76, P = .010). The primary patency was significantly lower in the subclavian-innominate vein subgroup, with a median primary patency of 4.5 (3-12.75) months, than in the nonsubclavian-innominate vein subgroup (8.5 [5-13] months; P = .005). The median duration of each PTA was 8 months for the first PTA, 7.5 months for the second PTA, and 5 months for the third PTA. There was no significant difference in the patency duration of repeated PTAs and the primary PTA (P = .389). CONCLUSIONS: The mother-child coaxial dual-catheter technique has a good success rate and acceptable primary patency in the treatment of hemodialysis patients with CVS or CVO. Repeated PTA is as effective as the primary PTA. CLINICAL IMPACT: This is the follow up report on the "Mother-Child" coaxial dual-catheter technique for percutaneous transluminal angioplasty of central vein stenosis or occlusion in hemodialysis patients since we first presented it in 2019. In this paper, we can see that the long-term patency rate of this technique for central venous disease is satisfactory, and repeated use of this technique does not affect the patency time. Compared with other literature reports, the surgical success rate of this technique is significantly improved. Therefore, this technique is worth popularizing in the treatment of central venous disease.

Bioinformatics Analysis Reveals Hub Genes That May Reduce Inflammation and Complications After Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB), though indispensable in many cardiac surgery procedures, has several undesirable consequences. The aim of this study was to identify potential genes that may reduce the inflammatory response and complications after CPB. The GSE132176 dataset was selected from the Gene Expression Omnibus (GEO) database and included 10 patients with tetralogy of Fallot and 10 patients with an atrial septal defect who underwent CPB surgery. TSV files were downloaded after GEO2R processing. Protein-protein interaction analysis of common differentially expressed genes (DEGs) was performed using the Search Tool for the Retrieval of Interacting Genes. Gene modules and hub genes were visualized in the protein-protein interaction network using Cytoscape. Enrichment analysis was performed for all important DEGs, modular genes, and hub genes. A total of 72 DEGs were screened, including two functional and one hub gene module. FOS modular genes were primarily enriched in NGF-stimulated transcription, spinal cord injury, and PID AP1 pathway. The ATF3 modular gene was mainly enriched in cytomegalovirus infection and transcriptional misregulation in cancer. Hub gene modules were primarily enriched in the PID AP1 pathway, positive regulation of pri-miRNA transcription by RNA polymerase II, and the PID ATF2 pathway. FOS, JUN, ATF3, and EGR1 were the four most important hub genes; the top three hub genes were involved in the formation of AP-1 and enriched in the AP-1 pathway. Finally, we measured the expression levels of these four genes in patients undergoing CPB via qRT-PCR, and the results were consistent with those obtained in bioinformatic analysis. FOS, JUN, ATF3, and EGR1 and the AP-1 pathway may play key roles in inflammation and complications caused by CPB.

Study on Fe-C-Al three-phase micro-electrolysis treatment of low concentration phosphorus wastewater.

In this study, the iron-carbon-aluminum (Fe-C-Al) composite filler was prepared by aluminum modification of conventional iron-carbon (Fe-C) micro-electrolysis with a no-burn method. The optimal process conditions for Fe-C-Al three-phase micro-electrolysis treatment of low concentration phosphorus wastewater were determined to be the aluminum metal ratio of 14 wt% and solids dosing of 30 g/L. Under the optimal process conditions, Fe-C-Al three-phase micro-electrolysis was performed for the treatment of low concentration phosphorus wastewater (LCPW) with continuous experiment, while iron-carbon fillers before and after treatment were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results showed that the amount of Fe2+ dissolved in the micro-electrolysis determined the micro-electrolysis phosphorus removal effect, Al promoted the dissolution of Fe2+, and the Fe-C-Al filler had a stable phosphorus removal effect, and the average removal efficiency of phosphorus was 67.40%, which is an average improvement of 29.25% compared with the conventional Fe-C filler. The treatment of LCPW by Fe-C-Al three-phase micro-electrolysis is consistent with a first-order kinetic reaction with apparent activation energy of 38.70 kJ·mol-1, which is controlled by the chemical reaction.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Role of long noncoding RNA taurine-upregulated gene 1 in cancers.

Long non-coding RNAs (lncRNAs) are a group of non-protein coding RNAs with a length of more than 200 bp. The lncRNA taurine up-regulated gene 1 (TUG1) is abnormally expressed in many human malignant cancers, where it acts as a competitive endogenous RNA (ceRNA), regulating gene expression by specifically sponging its corresponding microRNAs. In the present review, we summarised the current understanding of the role of lncRNA TUG1 in cancer cell proliferation, metastasis, angiogenesis, chemotherapeutic drug resistance, radiosensitivity, cell regulation, and cell glycolysis, as well as highlighting its potential application as a clinical biomarker or therapeutic target for malignant cancer. This review provides the basis for new research directions for lncRNA TUG1 in cancer prevention, diagnosis, and treatment.

Efficacy of ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis or occlusion at juxta-anastomosis: A 3-year follow-up cohort study.

OBJECTIVE: Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty (PTA) has become a choice for AVF stenosis, and ultrasound has been used in PTA more frequently. METHODS: This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2016. Angioplasty was performed using a noncompliant high-pressure balloon. The process was visualized by duplex scan. Our inclusion criteria were as follows: (1) stenoses or occlusions were located at the juxta-anastomosis site: the first 5 cm of the vein distal to the anastomosis; (2) stenosis was confirmed with the following conditions: (a) flow rates are <500 mL/min in the brachial artery and <200 mL/min in the fistula during dialysis, and (b) the stenosis diameter is <1.7 mm. We used the Kaplan-Meier curve to show the postintervention primary and secondary patency rates of patients with stenosis and occlusion. RESULTS: Altogether, 129 patients with 76 males were analyzed. Moreover, 104 have AVFs on the left arm, and only one patient had an ulnar-basilic AVF, whereas others had a radial-cephalic AVF. The postintervention primary patency rates are better in occlusion cases (P < .05), whereas secondary patency rates have no difference. The postintervention primary patency rates are better in patients without diabetes mellitus (P < .05), whereas the secondary patency rates had no difference. CONCLUSIONS: For juxta-anastomosis site stenosis or occlusion, PTA can be used to obtain satisfactory results.

A secreted pore-forming protein modulates cellular endolysosomes to augment antigen presentation.

Bacterial pore-forming toxin aerolysin-like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that ßγ-CAT, an aerolysin-like protein and trefoil factor complex identified in the frog Bombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation. The protein augmented the antigen uptake of dendritic cells and actively neutralized the acidification of cellular endocytic organelles to favor antigen presentation. In addition, the release of functional exosome-like extracellular vesicles was largely enhanced in the presence of ßγ-CAT. The cellular action of ßγ-CAT increased the number of major histocompatibility complex (MHC) I-ovalbumin and MHC II molecules on dendritic cell surfaces and the released exosome-like extracellular vesicles. An enhanced antigen presentation capacity of dendritic cell for priming of naive T cells was detected in the presence of ßγ-CAT. Collectively, these effects led to strong cytotoxic T lymphocyte responses and antigen-specific antibody responses. Our findings provide evidence that a vertebrate-secreted pore-forming protein can augment antigen presentation by directly modulating cellular endocytic and exocytic pathways, leading to robust activation of adaptive immunity.

Non-targeted proteomics of acute respiratory distress syndrome: clinical and research applications.

Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid with a high mortality rate, but the underlying mechanism is not yet fully understood, causing absent specific therapeutic drugs to treat with ARDS. In recent years, more and more studies have applied proteomics to ARDS. Non-targeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in this disease. This paper will provide a brief review of the recent advances in the application of non-targeted proteomics to ARDS.

Isolation and characterization of the major centipede allergen Sco m 5 from Scolopendra subspinipes mutilans.

BACKGROUND: Allergic reactions have been observed following both direct centipede bites and the clinical use of centipede-containing medicines, such as traditional Chinese medicines utilizing Scolopendra subspinipes mutilans; however, no natural centipede allergen has yet been characterized. METHODS: An allergen was purified from S. s. mutilans venom using Superdex 75 gel filtration and RESOURCE S ion chromatography, and its primary structure was determined via a combination of LC-MS-MS, MALDI-TOF/TOF and protein sequencing techniques. Its potential allergenicity was evaluated by immunoblotting, ELISAs, skin prick tests (SPTs) and mast cell activation assays. RESULTS: A novel allergen Sco m 5 (210 amino acids long) was successfully purified from crude S. s. mutilans venom. Sco m 5 could promote the degranulation of a human mast cell line, HMC-1. Among centipede-allergic patients, Sco m 5 showed an 83.3% IgE-binding frequency and a 66.7% positive reaction frequency, as detected by immunoblotting and SPTs, respectively. Sco m 5 IgE-binding frequencies of common Chinese population was found to be 9%-16%. Sera positive for Sco m 5 IgE-binding was cross-reactive against venom from the wasp Vespa mandaeinia. CONCLUSIONS: The present study isolated and characterized a novel allergen termed as Sco m 5 from the centipede S. s. mutilans. The use of Sco m 5 to identify centipede-allergic individuals could be important, given the high potential allergenicity of Sco m 5 among the general Chinese population, along with the likely possibility of cross-reactivity against wasp venom among centipede-allergic patients.

Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. ßγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (ß-subunit) complex (ßγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of ßγ-CAT on skin wound healing. ßγ-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarless healing. ßγ-CAT treatment resulted in a rapid release of IL-1ß, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF-ß1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after ßγ-CAT treatment. ßγ-CAT protected skin wounds against methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that ßγ-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin-like pore-forming proteins widely existing in plants and animals may act in wound healing and tissue repair.-Gao, Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.

The reduction of synovial tissue macrophages is a reliable biomarker for clinical improvement in patients with rheumatoid arthritis (RA), and macrophages are reduced in synovial tissue shortly after initiation of TNF inhibitors. The mechanism for this initial response is unclear. These studies were performed to identify the mechanisms responsible for the initial reduction of macrophages following TNF inhibition, positing that efflux to draining lymph nodes was involved. RA synovial tissue and synovial fluid macrophages expressed CCR7, which was increased in control macrophages following incubation with TNF-α. Human TNF transgenic (hTNF-Tg) mice were treated with infliximab after development of arthritis. Ankles were harvested and examined by histology, immunohistochemistry, quantitative RT-PCR, ELISA, and flow cytometry. hTNF-Tg mice treated with infliximab demonstrated significant clinical and histologic improvement 3 d after the initiation of therapy, at which time Ly6C+ macrophages were significantly reduced in the ankles. However, no evidence was identified to support a role of macrophage efflux to draining lymph nodes following treatment with infliximab. In contrast, apoptosis of Ly6C+ macrophages in the ankles and popliteal lymph nodes, decreased migration of monocytes into the ankles, and a reduction of CCL2 were identified following the initiation of infliximab. These observations demonstrate that Ly6C+ macrophage apoptosis and decreased ingress of circulating monocytes into the joint are responsible for the initial reduction of macrophages following infliximab treatment in hTNF-Tg mice.